Special episodes

Sally Best

Hello. You are listening to One in Two a Manchester Cancer research podcast brought to you by the University of Manchester and the Manchester Cancer Research Centre. With one in two of us receiving a cancer diagnosis at some point in our lifetime, it has never been more important for our research to improve the outcomes for people affected by cancer. I am your host, Sally Best, and throughout this series I will be speaking with Manchester cancer researchers about their innovations, discoveries and projects that are changing the landscape of early detection.

In this episode, we speak to Dr. Jen Davies Oliveira, a researcher and PhD student at the University of Manchester. And Stewart O'Callaghan, the founder and chief executive of Live Through This, the UK's only LGBTQIA+ cancer charity. We discussed: challenges that LGBTQIA+ people face when accessing cancer care in the UK; Jen's research project, an alternative cervical screening, which aims to tackle some of these inequalities and Stewart experiences. As a person living with cancer, how they came to set up their charity and how it is aligned with research.

Hello and welcome to our special episode. We've got Stewart and Jen. Say hello guys. How you feeling?

Stewart O’Callaghan

Yeah, Good.

Jen Davies Oliveira

Fantastic. It's Friday.

Sally Best

It’s Friday. How are you doing, Stewart?

Stewart O’Callaghan

Yeah, good. Long journey up. Train got stuck halfway. We just had to reverse back down the tracks to get back up again. But made it back to Manchester

Sally Best

Let's go on to introductions. So I'll start over here with Stewart, please. Could you introduce yourself? Who you are. What you do, your pronouns. Just a little synopsis.

Stewart O’Callaghan

Yeah. So my name's Stewart O’Callaghan. I use they them as pronouns. And I'm the founder and chief exec of Live Through This, which is the UK's only LGBTQIA+ cancer charity. I have set it up because I have chronic myeloid leukaemia and felt the difference that our community has first hand. And now we support patients, educate professionals and make new resources.

Sally Best

Fab, Jen

Jen Davies Oliveira

So I'm Jen Davis Oliveira. My pronouns are she her and I am a researcher at the University of Manchester, but also a gynaecologist. And I work so my PhD focuses on alternative cervical screening methods, including urine cell sampling. And I think that's pretty much it. I guess we'll find out a bit more as we go find as we go along.

Sally Best

We will. There's lots of things that you forget. You always get scared as well when you're doing your job description, like you're going to miss something out.

Jen Davies Oliveira

It's really interesting actually, because it was really easy when I was just a doctor, a gynaecologist. This is how many years of training I've done. This is how big the bags under my eyes are. And now I just see too many hats. So I, I get confused.

Sally Best

Too many hats you do. Well I'm Sally Best, she her and I am your podcast host. I am not a gynaecologist and I'm not a CEO, but I love speaking to them. So it's great. Stewart, I'm going to put you on the hot seat again. So you said that you've got chronic myeloid leukaemia. Yeah. What does that entail?

Stewart O’Callaghan

So it's a really rare blood cancer, super rare. And I got it when I was 29, which makes it even rarer. And for me, it's a disease that isn't curable, so it's managed. And I take medication pretty regularly. It's just an oral pill and I'm treated as an outpatient. But even with that, I've had that experience of people not really being able to offer me this support I was looking for and people not really understanding where my identity, sort of crossed over with the cancer experience and also just asking questions as well. My nurses and clinical team about my health and where things were going and just getting no real answers, which is what really drove me to go into this work. So previous to this, I was the tattooer for ten years, so it definitely was a bit of a shift. It is a good area and I think it's nice to be in an area like cancer care, thinking about inequalities and progress and that's why it's really nice to meet Jen and the work she tends to.

Sally Best

Yeah, and you're both a member of the LGBTQIA+ community? Which one of you wants the lovely job of telling us each one of those letters.

Jen Davies Oliveira

So I can start. So lesbian, gay, bisexual, transgender.

Sally Best

Intersex

Jen Davies Oliveira

Queer or questioning. Yeah intersex asexual asexuality and plus because of course people also identify as different as other identities and one would be pansexual for example.

Sally Best

So, Stewart, do you identify as queer?

Stewart O’Callaghan

Mm hmm.

Sally Best

Okay. So I'm just wondering if you could kind of explain your journey as a service user because you've got cancer. So, I mean, what's your treatment experience been on your journey from diagnosis to treatment as a queer person with cancer? What's that journey been like and what was your like, so stage of diagnosis to where you are now?

Stewart O’Callaghan

Yeah, so blood cancers are usually diagnosed in a bit of a rare way because of their symptoms and the way they show up. So it was, I weirdly had food poisoning, which didn't really resolve itself. So I had to go via A&E and that's when the blood work was off. But I was living in Germany at the time and it was an odd thing to sort of be diagnosed in a country where it's not your sort of natural language and you're trying to understand how this stuff works. So I made the decision that actually I should probably head back to England so I could have treatment in language I understood and find support I needed. But what that meant as well was actually stepping away from the support network I had because I built a life out there for my work. So I sort of came back almost needing more support than ever and went to Brighton in first case. And at that time I was really struggling with the side effects and treatment doesn't really agree with me, unfortunately. So it was, you know, having mobility issues and lots of other things. And when I went looking for support, I specifically said I need something LGBT. You know, I came out when I was 13. I've kind of grown up queer, as it were. It's my whole life. It's my community, it's what I know. And there was just nothing available, even in Brighton, which was shocking, you know? Yeah. And the things that they offered me was go play sport with the boys. And it's like, Well, not only can I not really walk, it's also not really going to work with me for other reasons. So it really did kind of leave me without support for quite a while. And then that was whilst I was failing different treatments, going on new ones being put in for trials. So there was quite a lot to handle. And the whole time I never really felt like I had an opportunity to speak to someone else from my community who maybe understood what was coming from, whether it be a different cancer or not, and it was actually taking part in someone else's research that gave me their first opportunity to talk about my identity and my disease at the same time. And from even just being in that research interview, it really made me understand the importance of being able to have both those concepts in one conversation. And that's what led me to think if I've gained so much from just this piece of research, maybe there's other people out there who feel as lonely as I do and will want to connect on the same thing. And now we've managed to make peer support and do that. And I've almost made my own trap because now I'm the CEO of the charity, so I can't be too friendly with them. This awkward step of professionalism. But it's really nice to be able to provide that service for other people so they don't feel so isolated.

Sally Best

And we'll come onto that. But I'm just interested, what was that research that you participated in?

Stewart O’Callaghan

So this was a piece of research that was all about LGBT people with chronic health conditions, and it's done by the Access Care team in King's College, and they have many different arms. I think it's just access care C if I'm remembering rightly. And then now they've made a document for clinicians which actually guides people through the right way to speak to patients in the way to support them, I think is called the ABC of CARE.

Sally Best

Okay so you were diagnosed in 2016 and the charity was set up in 2019. What was that journey and what was the inception of it and what inspired you and drove you to set up this charity? Because I mean, it's the only LGBTQIA+ supporting and advocating charity for cancer in the UK, which is just bizarre.

Stewart O’Callaghan

Yeah, I definitely feel like that. And I think that's what drove me to do. It was the lack of one being there, and it's the fact that as a patient sort of going out and asking these questions. Not every patient will have the confidence to come out to their care team to get that support. They maybe want to go away and look it up independently. That kind of thing. And whenever I was doing that, I didn't really find anything or if I found something, it was one small project that got de-funded within 12 months because it was on a limited thing. So I wanted to provide something that had a little bit more stability and reliability because I knew that's what I would be looking for. So I actually went to my Macmillan Centre and saw my treatment hospital. I had a really fantastic person that has now become a colleague, Lynsey Farthing.  I went in and kind of asked them a question I knew they couldn't answer, and I was like, do you have an LGBT service? And they didn’t, and they knew that. So I just propositioned them and said, do you wanna help me make one? And I was always grateful for the fact Lindsey just said, let's do this and gave me all the resource and support. And I think that's what's really helped see it going. And then as for turning it into a full charity, that wasn't the original intention, but somebody just on an offhand in that same Macmillan Centre said, have you thought about turning into a charity? And I had really thought about it, I've never been in the charity world. I didn't understand how it works, but I thought about it a bit longer. Did my reading. I understood what it meant and realised actually, yeah, it would take a big commitment of myself to do this, but also, I'm incurable, so there's no way I'm going to get away from my cancer. So why not do a lemon lemonade situation and see if I can build something out of it?

Sally Best

Yeah, so it's a great story and I think it's sometimes the projects that see the greatest fruition are those that are really personal to you. And it is personal to you, and we’ll kind of go onto barriers that are faced by people in this community, but first time experiencing them is a lot different to knowing that they exist.

Stewart O’Callaghan

Yeah, and I mean, it's something that people, especially in the clinical space, really welcome at this point. I think they've really embraced the idea of that expert by experience thing. But at the same time, although we do see that, we also see there is still a bit of a difference between the voices that get listened to in the expert by experience room. And typically, you know, they are people who have the resource to take time off in the middle of the day and sit in these rooms or, you know, so you start seeing the same demographics. Every single time.

Sally Best

Yeah

Stewart O’Callaghan

So I think there's also an acknowledgment we have to take that. You know, I sit as a bit of an exception in that. And I think people who might be listening or think you from a clinical point of view of like, oh that's great. I wonder what I could encourage in my local area. Make sure that you hear from voices that you maybe typically haven't heard from before when thinking about these things.

Sally Best

Yeah, and I mean this it's really shocking that you are the only charity of this nature that exists. Do you think that is just because of kind of previous exclusion?

Stewart O’Callaghan

I think I think inequalities in cancer is kind of a new thing still. It's a bit behind compared to other things. I was speaking to someone from the care environment recently who came into the cancer space and they were shocked by how sort of behind cancer was, which was quite interesting. And when I first started doing this work, I was told multiple times by people that there's no need for it. They've done it in the past. It didn't take off, you know, Macmillan did one event, no one cared, and then that was it. So I think people had tried before and there's been more small projects. But I think especially what I found, the commitment it takes to build something is extensive, it's exhausting. And in the same way, these things can be passion projects that can actually lead to burn out. So I think that's why when you see people doing good pieces of work, it helps to resource them, open doors, give them support, that kind of stuff. And I've been lucky to have that from certain people in the cancer space. But there definitely, I think in the beginning was a lot of disbelief as to this doesn't need to exist or, you know, this big charity's done this one LGBT project five years ago. You don't need to be here. But I think there's extra power in having a charity that's patient led. And it can have that view. And, and also, I'm not making the recommendations we do for the charity just off my personal experience. We're engaged in research, we’re plugged into the clinical sector. We're doing peer support, we're hearing directly from people. So we're always making sure that the direction we travel is what our beneficiaries want.

Sally Best

Yeah, and I think that's really key, research that benefits the community, not just personal interests and yeah, I mean, I think I'd like to go on that the way that people kind of view these minority groups as optional.

Stewart O’Callaghan

And I think something I've come to terms with recently is it's the pain of retrofit. So the way that the system’s been built, it hasn't been built for minority communities at all. So that's why it feels painful to retrofit them. And it takes more money and it takes more time and it feels uncomfortable. Whereas when we have the opportunity to be inclusive in our innovation, then we can futureproof things. This is why research like Jen's is so important, because it's making sure that it's inclusive at the nascent stage of us bringing in new potential techniques for screening and things like that. And I think that's what needs to happen more, making sure that we're inclusive from the start so we're not having to do this costly, painful retrofitting of services five, ten years down the line, when you realize it isn’t serving people. An example of that is the u- screen pilot in north east London with the self sample for HPV with the swab, and they based it on the call and re call register. So by definition it was excluding trans male patients because they were going off a system that already excludes them. But that was a blind spot they had. So they didn't do it maliciously. But it just shows again how if we don't really think about inclusion from the real beginning, we might potentially be missing really useful data to understand people who might benefit from these changes most.

Sally Best

And could you explain a bit more about that u-screen program and what you mean by the call and recall?

Stewart O’Callaghan

Oh yeah, sorry.

Sally Best

No don't worry. You're just very erudite and I'm like take it back a step.

Stewart O’Callaghan

So the call and recall system is the system by which we call people up for cervical screening. And it runs sort of in the background. And it's how you get your invitations via letter and you'll be sort of held on this list of you’re ready to be called because of certain age or gender markers, things like that. And people can be opted to take off that list. That prior notification is listed. For example, they have a hysterectomy, so they no longer have a cervix, it's no longer relevant. There's aspects like that. But actually getting yourself on the list isn’t really possible at the moment. There's an update that's working towards that. But so for people who are trans male and have reregistered their gender with the GP as male, that pulls them off the call and recall register because they have an entirely new NHS record. So they have to go in and speak to their GP and ask for that test, which is a multi-stage barrier, because then they have to disclose that they're trans, they have to then go in. There's also the barriers of if the lab accidentally refuses the sample because it's not registered as being a sample. There's all these steps and unfortunately the majority of these steps remain a burden on the patient. The patient has to drive all this stuff and that's where it becomes inequitable when you consider it to the cisgender female peers who get the automatic reminder. They don't have to put it in their calendars. You know, it comes into them. And that's not to say, you know, the process is pleasant for anybody. Yeah, but when we think about the access to the service, that's the bit that sometimes needs the revision, which is what NHS are trying to do in the background.

Sally Best

Yeah, and I guess not only is that process very arduous, but it's also kind of it might risk late diagnosis, an even further kind of issue with, with that. And I mean just touching on this. So is it the same for trans men that would have had breasts or maybe still have breast and have that haven't had their reconfiguration surgery? Would they be removed from the breast cancer screening?

Stewart O’Callaghan

Yeah. So how it works basically is if you reregister your gender with your GP, you get an entirely new NHS record. So what that means is now your let's say male record exists as any other standard male record in the medical system. So therefore, if there is a screening process that's based on a gender marker, you'll be excluded from it. So if we think about breast and cervical, so you are right, there are people at the moment who will be registered as male but still have adequate breast tissue for screening. And at the moment, again, they have to self advocate and I'm pretty sure they go through a systematic pathway at the moment. But their screening program is looking if they can make this system better. But it would still be a case of self advocacy. I think it is this aspect where the systems, as you said, a sort of built in this way, where they go off that sex marker and then when you get that new NHS record, there is that issue because we don't have the sex and gender markers on the record. It's just all consolidated into one. So that's why it can be pretty tricky about calling people up for the right tests. And it's also why patients need to understand when they do reregister their gender that this might happen. Yeah. So that if that burden is now on them, that they can make those points, but it's also part shared by their GP or by the breast clinics who, for example, think about cervical screening again, there are systems by which you can generate your own lists on EMIS or system one, whichever system you're using, so that it actually does flag and give you reminders of when to invite these patients in and take that extra process on. But it's just not all GP patient practices are doing it.

Sally Best

Okay, but that would be something that you'd advocate for.

Stewart O’Callaghan

Yeah. And Owen Carter from RM partners created a step by step process for EMIS, which you can access on the our partners websites. That's a cancer alliance in West London. And I recently spoke to a practice in Hebden Bridge who have done it for System One, and I'll be getting access to that too. So if anybody is on those systems and they want to know how to create those lists, the information's out there and just get in touch.

Sally Best

Okay. And did you work on a non gendered breast screening assessment? Breast assessment? Self-breast assessment.

Stewart O’Callaghan

Yes. So because the great breast screening program starts at 50 up, there's obviously a large proportion of people there who will want to be understanding what's normal for them. And when we think about people who access transition, that normal can change. Obviously, you might grow breasts, you might have them removed by top surgery. So it was really a campaign by which we could work with trans people to find out how do you want the information, what's going to work for you? And I naively went in and thought, Oh, let's do a trans male poster and a trans women's poster. And then when we did the focus group, they were like, why? Like what? You just falling into the same trap? And instead they just said to us, like, tell me the symptoms. Find me a way to see the symptoms without having to show me pictures of bodies and all these things because they also pointed out that if the body doesn't look like them, it's harder for them to know how they relate to the information if it is for them. So that's why we created the chest check 101 with Coppafeel and it's all fruit. And it's also really useful because if we think about, for example, these trans men who had top surgery, so they have that bilateral mastectomy with a masculine chest reconstruction, there's still some tissue that needs to be monitored for breast cancer, but they can't go into the standard screening because there wasn't enough tissue for the mammography. So they need to be thinking about if they do notice a change like a lump around the nipple or up into the armpit, things like that. So it was a project that was done with Coppafeel, but also with the community. We had a focus groups and multiple stages of development and I think that's why it's been so well received because people told us exactly what they wanted to see and we just delivered it to them.

Sally Best

Yeah, that's thing to remember there’s a patient at the end of everything isn't there.

Stewart O’Callaghan

Absolutely. And I'm like, and I think there's some hubris in the fact if you think you're going to go in and pick the amazing solution without actually speaking to the person who's going to use your solution, you're setting yourself up for a fail. You're much better thinking about co-production right from the beginning, and this is in research to all the way from the co planning stage rather than this is a product I've made.

Do you like it? Yeah, but that's not really co-production.

Sally Best

No, just kind of an aside from that. But say if there was a trans female that was taking hormones and she was transitioning, would that put her at greater risk of developing certain cancers?

Stewart O’Callaghan

Yes. So a greater amount of oestrogen circulating in the body obviously has some changes like growing breasts, things like that. And that obviously can increase your risk. If we think about a trans woman’s risk of breast cancer compared to cisgender man, it's about 46 times greater. So that sounds like quite a lot.

Sally Best

Yeah it does

Stewart O’Callaghan

But it's actually a little bit lower than cisgender women. So and when breast cancer is identified, it seems to have quite a female pattern. So this is why they say that trans women can access breast screening as a standard. And obviously those who have reregistered their gender as female on the record will be automatically called as standard. So actually the process works pretty well. But when it does work and someone gets caught automatically and they go in, they have a good experience, it can be incredibly affirming. So in our campaign, Best For My Chest, we have Sophie in the campaign and she talks very openly about before transition. She didn't really feel connected to her body, didn't wanna look after it, and actually transitioning made her really understand the love she had for her personhood, the way she wants to look after her body and attending screening and being treated properly was really affirming for her and made her have a really fantastic experience which is going to then tell her to tell her friends and encourage people to go, which is a much better outcome than if, for example, someone had been, you know, maybe not so accepting of Sophie and then she would never go again when it’s a screening she should absolutely be accessing.

Sally Best

Yeah, 100%. And yeah, it's now part of her anatomy, which is really important. Kind of taking a bit of a backtrack, I'd like to just ask both of you about some of the barriers in cervical screening that LGBTQIA+ people might experience

Jen Davies Oliveira

I mean obviously there's universal barriers, so the three main ones are access. So for everybody that is, so actually going to your GP, finding time to do that, going in and having it done when you're not on your period, etc.. So there's a lot of access barriers there. But of course some people feel embarrassed about having an intimate examination and then they also feel discomfort or pain and obviously that ranges.

So some people don't feel any discomfort or pain at all. In some people it's really severe. So there's a really there's a big spectrum there. So those would be the main general barriers for absolutely everyone who is having this test, but specifically for our community, the LGBTQIA+ community, I would say that. So it's really interesting, the research that we've done, asking people about barriers. So we had 503 completed responses, just under half identified as transgender and half as cisgender. So if we sort of separate those two groups out, obviously the embarrassment, the access and the pain were there amongst the top barriers. But what was really interesting is in the transgender population, it was a lot about the provider. So in terms of being misgendered, so they'll go up to the to the person at the front desk in the GP and they'll go, I'm here for my cervical screening or to be with a nurse. And they'll go, I think you're in the wrong appointment. So just throwaway comments like that. So that's being misgendered, being in the waiting area that's full of pink, which is a colour that's very much associated obviously with, with the female gender. So that really puts people off not having LGBTQIA+ sort of if you have a flag on the wall or some material that shows that you're a friendly practice. So all of these things are big barriers, but specifically for the transgender population and then more within the cisgender population, it's more about those common barriers, but also not being able to share, you know, what their identity is as well, or feeling that like they can't be open about that.

Sally Best

And so I know you've spoken on this podcast before, but some people might not have listened to the episode, but they definitely should. But I mean, could you just give us a bit more of an overview about what your project is kind of looking at in terms of addressing these barriers.

Jen Davies Oliveira

Yes so my Ph.D. as a whole, its looking actually at urine testing instead of this this test that we do now, which is a speculum examination. This is a plastic instrument that we pop inside the vagina. And then we look at the cervix and take a sample from the cervix. And that's how cervical screening currently works. And, you know, I'm sure I speak for everyone, even though I'm a gynaecologist, I still find it a strange examination to have done personally. And I think it is a difficult one because you feel very vulnerable and obviously all the other things that we've just spoken about. So that's how it's currently done. And unfortunately we've just dipped under 70% of the population actually going for a screen. And we know that cervical screening, this process has reduced the number of deaths in the UK since the 1980s from cervical cancer by up to 70%, and it could be higher if we had a higher screening coverage. So we know it works, but it's just a case of how do we get people screened. So I'm looking at a urine test because now we test for the virus known as human papillomavirus. The high risk strains of the virus which you have to have to have cervical cancer. However, 80% of the population will have human papilloma virus at some point, but the majority will clear it. But there are a few where that virus will interact with their cervical cells and cause a cancer. And it does take a long time. So it takes 15 to 20 years for that cancer to develop. So we've got time. So that's why screening works really well. And the intervals are three years in England, five years in Wales, because we know we can actually make it a bit longer. I feel like I've gone off tangent.

Sally Best

Don’t worry.

Jen Davies Oliveira

So essentially, yes, my research is looking at a urine test testing for that virus because that's what the cervical sample does. So we're just trying to compare the two. So I've done a big study looking at comparing and looking at test accuracy and it's looking promising. So it looks like urine could detect the virus just as well as a cervical sample. And of course, that gets rid of that first initial barrier for the majority of people, which is the examination.

Sally Best

Yeah.

Jen Davies Oliveira

And also on top of that, we can also send it to people's houses and they can just do it at home. So second barrier gone, which is the access barrier. So that's, that's the sort of bulk of my research. But essentially a few people from the Christie came to me and said, this research sounds interesting. We would like to be more inclusive. Why don't we do some research within the LGBTQIA+ community? So it actually came from a few other people. And of course the research I was doing and I said, well, you know, the literature is not there's not much out there. We don't know much about cervical screening within the LGBTQIA+ community. We know a bit, there was a bit of research in 2013 actually in Manchester with 500 lesbian and bisexual women, and we know that they were less likely to go for screening. But it's not a huge population. And of course, within the transgender community, most of the research comes from the USA and that's of course very different because they have to pay for these things and there's insurance involved, etc.. So but we do know that we you know, we're pretty certain that they're less likely to go for screening, the whole community as a whole. And of course, lesbians and bisexuals, partly because well lesbians mainly they were misinformed. I mean, when would that have been? Stewart? I'm not sure. Maybe sort of.

Stewart O’Callaghan

I still hear about it now.

Sally Best

Yeah. I asked you this question the other day.

Jen Davies Oliveira

Did I not have the answer?

Sally Best

You did have the answer. But you're going to go on to explain that.

Jen Davies Oliveira

I mean, but there was there's a lot of misinformation saying that because you're not having because you're a lesbian and therefore, you know, the assumption is you're not having sex with a man then you would not be at risk of cervical cancer, which is, of course, completely incorrect. Anybody who's sexually active really is at risk. Pretty much everyone. I mean, I would say absolutely everyone is at risk. You know, it's really important that everyone goes for screening. So this misinformation meant that less people who identified as lesbian went for screening. And so therefore, you know, these people have been failed really with misinformation from the health care system over the past 10, 20 years. So, yeah, so it came from a few people coming, a few of us coming together and me saying, well, this test is looking good and this could really address barriers for this community. Let's explore them. And so, yes, we went about looking at how acceptable would a urine screening test be to this community, who we know are less likely to go for screening? So if we can increase the number of people being screened, that would be fantastic. Yeah. So that's how we went about it. And we really wanted to collect data on kind of knowledge around HPV because we know there's a lot of misinformation about the virus and whether it causes cervical cancer and also barriers, specific barriers and also general barriers, things that could help people go for screening and also specifically looking at cell sampling methods. And obviously, we've spoken so there's two different ones you can do vaginal sampling or and I think I've described it quite a few times now as like a COVID swab for the vagina. And you can also do that at home. And that's something that will probably become a reality for us in the next few years and an option. And Stewart just talked about the u- screen study. So they are looking at vaginal cell sampling and urine sampling. So that's the research that we are doing.

Sally Best

So on the on the u- screen, that was done in east and west London.

Stewart O’Callaghan

North east, I think north east.

Sally Best

Okay. And that was looking at the acceptability of vaginal swabs.

Jen Davies Oliveira

So it's looking as well as the feasibility. Okay. So essentially, if we're going to roll out vaginal cell sampling as part of cervical screening, then we need to know that it works on a big scale. Yeah. So that's what u- screen are doing. And actually we have the same thing in Manchester being done, so called HP Validate. So these two studies are going to inform this a medical screening program here in in England and in the whole of the UK as to whether we can introduce vaginal self sampling as part of the screening, the national screening program.

Sally Best

Okay. And with that, so there's nine other countries worldwide that use this. Why the heck isn't it here?

Jen Davies Oliveira

I know. I mean, I think we're behind. I think I was on a meeting, so we were part of it. So we know that the World Health Organization launched in 2019, a campaign to eliminate HPV, eliminate cervical cancer, because we know it's caused by a virus, we can vaccinate against it and we can screen against it and treat people with precancerous disease and therefore, you know, eliminate the disease. So there's a coalition that is started in the UK called the HPV Coalition. And, you know, with fantastic people in that amazing people that are doing amazing work across the whole spectrum of HPV work. So not just cervical cancer, because we know that HPV also causes other types of cancer. So I can go through that. So we've got also we've got vaginal and vulval the less common. So all the rest of these cancers are less common than cervical. So that's why we know about cervical. We've got anal, we've got penile and also oropharyngeal, which is the mouth and the throat and any I've missed? So this coalition has been started and within that coalition are stakeholders such as the Eve Appeal who are a charity that deal with gynaecological cancers and Jo’s Cervical Cancer Trust as well. And they were just saying, why haven't we why haven't we got self sampling all these people keep contacting them going, can I do a self sample? So everyone I mean, so Professor Crosbie as well, who's leading on this research, keeps getting emails and messages going. I can't have a cervical screening in the way that it's being done currently. Can I give a urine sample? So there's a real you know, there's a real drive for it. It's just that we need to. Need to get it done. But the problem is you have to sometimes jump through all these hoops to make that happen. But these two studies, you know, they are being done. They're almost I mean, I think that they'll be reported soon. And I think next the middle of next year, I think, is when they'll be looking at the evidence and deciding whether we can move forward with cell sampling. And urine will be part of that discussion. But we're a little way behind UK sampling.

Sally Best

So that's a kind of answer to those people that are saying, Jen, when is it going to be available? And when I say people, I mean me.

Jen Davies Oliveira

Yeah, I mean, hopefully in two years.

Sally Best

When you called out to this community, you use the term people with a cervix.

Jen Davies Oliveira

Correct.

Sally Best

Please, could you explain to me why?

Jen Davies Oliveira

The LGBTQIA+ community is really heterogeneous, right? There's a really you know, it's such a diverse group in itself being and you could argue being all lumped together. But there's a reason for that. You know, we, you know, it's a community that is minoritized, has been discriminated against. And, you know, I think we feel solidarity with each other. But I decided that I think it's really important just to a lot of the barriers that we face are all are similar. They're the same. There are few different ones. So we decided to keep it broad and we had you know, we did do co-production from the beginning that Stewart was talking about. And I think, you know, I'm so glad that we did that because it just meant that from the very beginning I really didn’t have an idea of how it was going to go. I mean, obviously you read the literature, but I wanted to hear from the community and it was a mix of people all across and they were very happy for this to be a community project. So we kept it like that. But of course, you know, within that survey, almost half of respondents identified as transgender. And of course we know that percentage wise of the population, you've got 10% who identify as LGB mainly. And then from a transgender perspective, it's about 1 to 2%. So it's a much smaller percentage. And yet we were finding that half of respondents actually identifying as transgender, which just shows how important it is to that specific subset of individuals. And of course, you know, most people who are transgender will not identify obviously as being a woman. And so therefore, we felt it was really important to use inclusive language, which obviously we discussed from the beginning by co-producing it with our group that it was important to be really inclusive in the language. And so we then used, I guess, more of a clinical term in many ways, but people or person with a cervix which is clinically correct but also very inclusive of people who do not identify as a woman. And of course we were specifically targeting transgender individuals within this piece of research.

Sally Best

And so is that where exclusive language, additive language and then inclusive language is that how it goes?

Stewart O’Callaghan

That's how I tend to talk about it. So it's a kind of your standard language, which is which you typically see. So, you know, say, for example, we talk about breast screening. It's kind of same as cervical. So for example, you take really, but if you would just say women of this age should go for screening and that's fine. And so that’s we see all the time, but as you touched on, it actually misses out potentially trans people and other gender diverse people who may need to access that service may not identify in the same way. And also it doesn't really give a lot clinical accuracy if someone's potentially had that piece of anatomy surgically removed. Yeah, so someone's had a hysterectomy or if they've had a mastectomy because if that if that's the case, want to go for the screenings. So again, it's all about eligibility and especially when we're talking about access to these services and also research, you have to be very, very clear about these things because they are your inclusion exclusion criteria. So then you have the additive language point, which is women and trans people or women and non-binary people, and some people use that and especially you see this more commonly in charities that have a history with women's health as a topic. They also go for this part and that's fine. Some people use it. For me, my preference is kind of the new NHS way because the ‘women and’ has this other ring. It kind of has this idea of like this is, you know, our main focus, but potentially those are these other people.

Sally Best

Yeah.

Stewart O’Callaghan

So I really like the NHS. This new approach which you can see on their web pages. CRUK also does this and Macmillan is moving towards it. So it's obviously like the way people are moving and it just speaks directly to the person. Yeah, if you have breasts and if you are between these ages you should get screened.

If you have a cervix and you're between these ages, you should get screened. You know if you have a breast and you’re between these parameters set by this study. Come and have a chat with us.

Sally Best

Yeah.

Stewart O’Callaghan

And then that leaves it to the person. You're not telling them how to identify and if you want to so there are no words being forgotten, you can add a, you know, supplementary statement. This might include women, trans and non-binary people. So there's no one being left behind. But then it saves you making an assumption on who that person is and the eligibility to what you're doing. And you get to be quite specific about actually, this is where we're going with this. This is what it's about and this is what it pertains to.

Sally Best

Yeah, And I think again, to echo there is nothing more dangerous than excluding people from screening.

Stewart O’Callaghan

Absolutely. You know, this is life saving stuff. Yeah. You know, so I also work like Jens provides a new direction, right? Yeah. We touched a little bit on inclusive innovation, but also there is ample existing messaging that's in the standard format that we've just touched on. So, Jen, adding something new doesn't remove any of the pre-existing standard language. So you still have legacy campaigns from Jo's trust from Eve Appeal and so on. And even these large charities have very inclusive language. Eve Appeal did the fantastic HPV has no gender documents, you know, so it's this understanding that, again, screenings for everybody provided you have the anatomy and ability to attend. And if you do, you shouldn't be excluded by this messaging and be left wondering if it's for you and the same goes the other way. So, you know, if you say, you know, women of this age need to go for screening and they say a trans woman wouldn't need to go for cervical screening. She doesn't have a cervix. But if she gets that letter from the automatic invitation, she might be confused. So, again, it's that ability to be very specific or at the very least, have the clinicians who are running these things understand the ins and outs of the eligibility so we're not accidentally including people in our appointments or research that shouldn’t be.

Sally Best

Yeah, I think that's one thing that I want to pick up in a bit is the health care practitioner education.

Stewart O’Callaghan

And I think generally there's the other issue when we do see LGBT stories in health education, it's usually HIV. Or it's sexual health based. It doesn't really go beyond that, which is why even as us as a charity, we meet people all the time. We have to tell them why we exist because they've never thought about pairing these two things together. Yeah. Whereas as Jen points out, if you read the research, it's obvious that we don't attend screening at the same rates, we’re less likely to go to the GP if we have a symptom, you know, we have barriers of access, especially for trans people who have reregistered their gender, there's myriad reasons why someone might not be getting screened in the same way.

Sally Best

Yeah, and I'd like to come on to that in a bit, but we have the two of you and we've not quite tied the knot as to why we've got both of you in the room. So how are you involved in Jen’s research?

Stewart O’Callaghan

So the way Jen and I met was kind of an interesting one. So basically Jen got in touch because Jen was doing an event to launch her research in Manchester. Or some studies about it with results and with the community.

Jen Davies Oliveira

It was an onsite cancer event about cervical screening in the transgender community online.

Stewart O’Callaghan

So we sort of had been aware of each other and we had a couple of emails and bits and bobs and Jen got in touch and said, I'm doing this thing and we’re looking for people on the panel, who do you want to be on it? Well me obviously.

Jen Davies Oliveira

Of course I lucked out.

Sally Best

So he’s standing right here.

Jen Davies Oliveira

Actually, this is not true. You actually suggested someone else initially because you're very humble. Very modest.

Stewart O’Callaghan

And so I travelled up and I was so impressed not only by the work and the quality of the work and the findings and the number of participants, which I think can't be understated. It's quite hard to get a large number our population to take part in research. So that's fantastic. But the research was cool. I'm really interested in urine HPV, because I really like that idea of inclusion and innovation. So it was like ticking all these boxes. But the other thing that I thought was so fantastic was that it felt like a community event. Yeah. And I'm, you know, a patient as well as a professional. And I sit on both sides. And I also do community work on the LGBT sort of side, and it's so rare to see those worlds come together and the way Jen’s event worked in that way was just it's left a massive impact on me. It's changed the way that I work moving forwards. It really makes me see the benefit of bringing people in and launching stuff in a community space in a nice feeling. You know, it even had performances from people who were on the panel. It just felt like a really good way that also not only updated people about research, but also then made them feel that the research felt accessible, safe. They had a stake in its direction and they'd be probably more likely to engage with self-screening when it comes to market. So for all those reasons, that's kind of what got me, I think, more invested in Jen, as it were.

Jen Davies Oliveira

It’s just really interesting how things happen. And sometimes when things happen, you don't realize what impact that's going to have. And so, for example, the survey itself, I mean, it was an incredible response. I'm not quite sure how we managed it, but I genuinely think that it just shows how important this research is to our community. It's just so important, which I didn't I didn't think that the impact would be that big. So that was the first thing. And then the second thing is that one of the people who is part of part of our study team, Emma Thorpe, it was actually through a family contact who worked for Manchester Pride that we were able to then access the amazing resource and events company that is Manchester Pride. I mean just incredible. And they were also really enthusiastic about the project and were happy to work on it and have a team on it. And we could never have dreamed about having, you know, such a beautifully done professional event. And it's really interesting for me as a like from a personal journey, I think I've experienced a lot of shame for my identity and I think we can all you know, we can all relate to that. You know, I'm a Welsh girl from the middle of nowhere, I had sheep to speak to when I was younger, you know.

Sally Best

Better company.

Jen Davies Oliveira

Yeah. So and I mean, it's the kind of place where when I came out to my family, they were just like, Well, you're the only person which is quite funny because, of course, you know.

Sally Best

You weren’t .

Jen Davies Oliveira

I wasn't. And I was like, But what about her up the road and what about him? So, you know, I've experienced a lot of shame for my identity. And it was really interesting because actually this work has really given me so much personally in terms of connecting with my community, which I didn't think, you know, I just didn't envisage that would happen. And the event felt like a big hug from the community to me and from me to my community. So it was very self-affirming for me, extremely, and it was very moving. I found it, yeah, really fantastic. So and that's how Stewart and I met. And then so Stewart also works with Alison Berner, who is an incredible clinician and researcher. Watch this space for further research looking at alternative methods of cervical sampling within the LGBTQIA+ community.

Sally Best

Interesting, Alison Berner bloody wonderful isn’t she.

Stewart O’Callaghan

Fantastic isn’t she. And there's another point about this innovation and screening as well that I think is really good. So when we do work for our community, there's also the benefits that it helps others as well. So it's this extra weight that moves forward. The idea that this is acceptable, it does work and it can work for people that need, for example, who may be trans or maybe have that, you know, vaginal atrophy after taking testosterone. So that makes speculum insertion more uncomfortable, for people who are survivors of sexual assault and have vaginismus. You know, there's like all these different things that actually just add further weight to the fact that self samplings, great. You can do it at home and not every person will want to do it. Some people won't feel confident and they want to go to their clinician and that's absolutely fine. I don't think it will completely take over the market. It's just another option to empower people to access lifesaving screening.

Sally Best

Yeah, well, that was going to be my next question. Like what other communities could this potentially benefit? And like you say, you know, sexual assault survivors, the idea of having an intimate examination must be really, really triggering. So, I mean, I know your research is very much founded in this one community, but the breadth of it and the ability of it to kind of encompass people that have been through trauma is just unbelievable.

Stewart O’Callaghan

Another one is modesty. For some, yeah, it may be a case of modesty. So therefore they want to be able to do it at home, you know, and also the other one that Jen touched on right at the beginning is if you have time. You know, Jen obviously is talking about that in relation to getting time off work and also fitting around your menstrual cycle and all these things, but also Jo's Trust just did the whole campaign of trying to get employers to let you take time off to go get screened. Yeah, so, you know, so it's obviously a real barrier. So the more we can give it to people so they can do it on their own time and send it back, which we've done in all of the spaces like sexual health have this where you can order a kit. So we should absolutely be moving forwards for it for screening.

Jen Davies Oliveira

And also caregivers as well, you know, people who don't have time because they have children or they have people who they have to look after. And it's just so difficult to find time, go and have that screen. And then if it's a little bit delayed, which unfortunately, you know, that we have pressed services, you know, then that takes even longer. And we talked about the practical things like not being able to have it at that certain time of months, etc.. So there's a lot of barriers there. And also, of course, we've just gone through a pandemic times I don't know how many waves did we have and of course that we know that the evidence shows that, you know, there's going to be an increase in the number of those with cervical cancer. Because we had a six month hiatus in screening for some parts of the country. So you know, this is an ample, perfect opportunity to be able to screen, but with no face to face contact. And just be able to send that out and send it back to the lab and that's it and get a and get a result. And then we know who's at risk and who isn't.. And who needs further investigation rather than, you know, having to go and have that face to face contact, that appointment and, you know, who knows in the future. Hopefully not. But we may get further pandemics. I mean, that's what's predicted. And so therefore, this would be a really good backup to ensuring that people that we don't get that increase in cervical cancer cases.

Sally Best

Yeah. And like you said, Stewart, it's not here to replace. It's there to include. So those people that feel really comfortable about going to their GP, speaking to them, having that face to face contact, that option will always be available to them. But it's, it's that, you know, that additive that's really, really important for people. Yeah, it's great. And I mean, I know I might be speaking with an echo chamber effect, but a lot of people that I speak to that my age, which is like 24, 25. But yeah, speaking to them just about this, it's like the question is, Jen, when is it available? Because, you know, I don't think it's positive that there's this kind of prevalence and dissemination, that cervical screening is a horror because a lot of people don't find it a horror. But then for some people, it really, really is the thing that there's just major barriers. And the thought of going for cervical screening is just beyond them because it's so traumatic. So, you know, you're really helping people here you guys.

Jen Davies Oliveira

We’ll give credit to Professor Crosby.

Sally Best

The gynae goddess. Lets give her some applause. And I mean, just back to the question that I kind of flagged earlier. So rebuilding systems for inclusion of minorities and it's often seen as an option. What would both of your responses be to that? Because it comes up quite a bit. I've witnessed it coming up, and I kind of am, in my opinion. I'm like, well, what is a minority to you? But I mean, what is your take on that?

Jen Davies Oliveira

It's an option or an afterthought, right? Those are the two things.

Stewart O’Callaghan

Yeah. Yeah. And I know and obviously any time that you don't provide equitable health care, you're creating poor outcomes for that community. And I think we've moved past the stage of that being almost ignorance and accident. And now it's got to the point where we have the data, we have community voice, we have these things, we have people, we have co-production, we have these tools. So any further exclusion feels more active. Therefore it needs to be addressed. And there is amazing work that's always going on in these areas too. So obviously the data was never going to stack up against the huge national registries we have and things like that. So that sometimes can be one of the things that's used, especially against the LGBT community when it comes to research. You know, you don't have the numbers. We can't make these suggestions, that kind of thing. But when NHS fails to record sexual orientation or trans status in its clinical records, we'll never have those numbers. But that doesn't mean we shouldn't be making progress.

Sally Best

Yeah.

Stewart O’Callaghan

So it's thinking again on that bigger picture. And I think for too long cancer care has seen equality in silos its seen it in ethnicity and race, and it's seen it in disability and it's seen in other aspects. And actually when you bring all these voices together, we tend to converge on common themes and common recommendations. And I think there is something to be said about Jen's work and people like Jen because it's also building community understanding and trust in screening, what it is, how it works. People even currently don't understand what the existing format of cervical screening really does, but we need people to understand what these innovations are when they come in so they're more likely to take them up.

And we saw this from Wales and increase that window between appointments and there was a lot of confusion and fear about it. So I think when we think about this stuff, it's thinking about how do we make the research inclusive. So do we have representative samples, How do we make this administration inclusive? Are we relying on existing systems or do we need to build a new one? And also, how do we make the messaging inclusive, speaking to people in a way that they understand? Are we using language that they recognize? And that's also when we think about people who have English as a second language. Yeah, people with learning disabilities, aspects like that. So they can still access these innovations and they're not almost ring fenced for people who are the sort of majority patient.

Sally Best

Yeah.

Jen Davies Oliveira

You know, one of the things that I guess I'm quite proud of is that in our so, in my general work within the colposcopy clinic, our initial survey of acceptability of urine sampling didn't have anything on it related to gender identity and sexual identity. So we added that. And I just think it's really powerful watching people fill that out. I mean, obviously, you know, you're not meant to, you know, it's just me and that person in the room. But it's really interesting because it stimulates discussion even amongst people who don't identify in that way. And some people like giggle a bit. You know, it makes them feel a bit uncomfortable, you know, and maybe go oh, why is this here? But I mean, even if that is the reaction, the reaction may be a negative one is your, you know, is your gender the same gender is as you were assigned at birth, for example, is a question. But it's it is stimulating discussion and making people think and go, oh, actually, yeah, okay. So there are there are people who may take part in this research, i.e. have a cervix. Yeah. And actually, you know, not identify as a, as a woman. Yeah. So that's been really powerful. So I, you know, from a research perspective, I always tell people, you know don't be scared of people being offended. You know, my research also has about 20% of individuals who identify as in a, in an ethnic minority group. And the research also is about 10% that identify as LGBTQIA+ which is great because that's, you know, that's how many you know, that's a percentage within the general population. So, you know, and people are often worried that there's going to be, we're going to offend different people from different cultures, etcetera, etcetera. But I just think we just have to normalise it in some way but make it visible, you know, we can't just ignore it and go, Well, this isn't an issue any more. We need it to be there and obvious. But and by doing that, we're normalizing the conversation and saying, yeah, we exist, we're always going to exist, we always have existed. And, you know, we deserve a voice just like anybody else. Any other human being.

Sally Best

Could you tell me about your work on Inclusive pregnancy status? IPS

Stewart O’Callaghan

Oh, yeah, of course. Yeah. Yeah. I was wondering where that was going to go there. So the IPS is the inclusive pregnancy status, and it's something that I co-wrote with the Society of Radiographers. And basically Lizzie gets the credit. Actually, Lizzie started this, Lizzie Scott and she's an advanced therapeutic radiographer. If I'm remembering this correctly, and in Leeds and was looking at, well, why don't we have a way to really support this questioning of who's coming in when they're having diagnostic psychotherapeutic radiography? How do we check they're not pregnant? And a lot of it got inspired by the fact that there was a CQC report, I think it was, of a trans guy who was irradiated, pregnant because no one had asked the question. And that's kind of where it comes down to. IRMER, so that's your radiation law. And on IRMER, it basically says, its quite gender neutral in it's language, it says that we should be making inquiries for people with the potential for pregnancy within certain age limits and however, it doesn't really give you any guidance on how to do that. Then the RCR kind of did a document afterwards that gave suggestions, but again, wasn't very specific, but it basically said it's up to local people to figure out how they're going to do that. So what the IPS does is it gives people a tool to do that safely and effectively. So what we have is we have forms that allow people to, as Jen was touching on, give questions about sexuality at birth and things like that. So they might be able to share that information. There's a very long document of guidance that talks through why this exists in the first place and talks through the clinical examples. It goes over things like not only the issue of making sure we check someone's potential for pregnancy, but also some myths that exist in the community that testosterone is a contraceptive when it's not. And also making sure as well that patients feel safe to disclose and that the clinicians understand why they're asking it, too. Yeah, because when you give a tool to people in practice, they're not going to use it unless they understand the benefit because it's just going to feel like one more thing to do in a busy clinic.

So we did we did like little test runs, as it were, in different clinics, and it went down really well. You know, I think there's a lot of fear about where people understand the form, you know, will people get offended. And actually it went down super well. And then once we'd done that and we got some data, we finished writing up and sent it out. And it again is just this aspect of the little extra tick box is going to potentially improve people's lives. That's, that's the outcome.

Sally Best

You’ve discussed about how you're informing people to ask that right question and ask the question that's potentially going to save lives or save a life. How have you been working with health care practitioners on kind of inclusion of studies such as Jen into adoption, into general health care?

Stewart O’Callaghan

So if we take the IPS example, you know, we understood that you can't just release this quite heavy document and send it out and expect people to just, you know, lap it up and put it straight to practice. And ultimately because it's a piece of guidance, it's, you know, from them it means it's somewhat optional if people want to take it up. So the way that works is and you have to educate people, why does it exist? How do you implement it? And we did a webinar, you know, and it was super well-attended and it was hosted by the SOR. And it just shows that you have to kind of you have to take a multi-level approach, you have to engage people, you have to check what they want, you have to check their existing practice, you have to see how you can shift it ever so slightly, so you get the change you want without completely rewriting the whole process. And then you have to educate them on why you've done it. You have to almost cover all your angles and make sure they understand why it exists and that it's been well researched. And then, you know, also have your back channels for evaluation and all these kind of things. So we did that. As a charity, we also provide webinars to health care providers so that they understand where LGBT identity intersects with cancer experience. We do that from a cancer patient experience point of view. We also do it from the clinical incident point of view. So when we talk about cancer risk modulation as a result of excision, it's hormone use, those kind of things or, you know, vaginal atrophy from long term testosterone therapy and how that might change the sample taking. So it's those things I think, sometimes really excite clinicians because they understand that actually there's something clinical going on here. It's not just the zeitgeist of wear a rainbow badge pin, which is part of the puzzle.

Sally Best

Yeah.

Stewart O’Callaghan

But there’s actually something here that is about patient outcomes.

Sally Best

Yeah.

Stewart O’Callaghan

And we touched on it earlier as well about sexual wellness, checking with the patient about their sexual plan. And if we think about the attention given to queer women in regards to sexual wellness going through treatment and coming out, whether that's radiotherapy or surgery, the lack of attention and support they have and the lack of research to support them is shocking. There is a fantastic PHD out there by someone called Joy Hall who I’ve have spoken to recently and it's something that Lizzie again from the IPS is exploring, but it's this idea of why do we have these gaps? Why isn't it a priority? These people are out there. They absolutely deserve answers like everybody else does. So there's a long rambling answer.

It's about connecting the whole picture. Clinicians in the field who are really trying new things, including best practice, third sector, patient voice, people like Jen doing research that's at the cutting edge of innovation, evaluating the existing pitfalls, all of that stuff. And the more that the cancer sector speaks to each other in this way, the more that we can create a solution that works for everybody rather than it feeling like one person's gone rogue.

Sally Best

Yeah, exactly. And there's not just that path of research to patient. There's a hell of a lot involvement behind the scenes.

Stewart O’Callaghan

And that path is so long.

Sally Best

Yeah. Yeah.

Stewart O’Callaghan

So, you know, I used to be such a long time ago before the charity thing. And the thing that frustrated me most was you come up with a fantastic theory, but it's never going to reach people for five, ten years. So that's why sometimes it's useful to bring in these ideas of co-production and community involvement and this kind of stuff, because not only does it help them feel like it's a tangible thing on the horizon, but it also creates that momentum and drive for clinical services to adopt the change because they have a subset of general population who are willing to take up this this new direction.

Sally Best

How do you envisage your research kind of getting into that health care continuum, do you think work with Stewart?

Jen Davies Oliveira

Yes, for sure. I think for me I'm really I mean, I've still got some research to do, so I'm about to start some interviews. So delving deeper into the acceptability of cell sampling, urine sampling for cervical screening in this community. So really excited about starting that work because it's also part of my learning process. And I think it's going to be really interesting to be able to have these conversations that are more personal than just a survey. So we'll be able to put those two things together and get a real sense of what our community want from screening, which is going to be so powerful and be able to shape the future of cervical screening in this country. I mean, that's what's incredible about it as a community where we've not had a voice in so many things because we're always an afterthought or just not thought about.

So it's really exciting to be doing that. And obviously I'm sure there will be more work being done in this space with our communities.

Sally Best

And Stewart, coming to you as kind of a hope for the future, what are the hopes for a future of Live Through This?

Stewart O’Callaghan

So for me, it's making sure we reach more patients so they don't feel so alone like I did for so many years. And we know we're reaching new people. Every month people get signed up to our peer services. But, you know, if ever there's a patient out there, absolutely. Get in touch. We continue to educate health care providers, making sure that they feel confident to provide good care so that it reduces the negative experiences people have when they find us, obviously, and we continue to put out new information.

So that people have campaigns that speak to them, they're likely to access things. And then watching people like Jen with great interest about where the research is going and making sure that we can then as a charity, help amplify the message when this you're in self screening or self sampling finally comes to market and we can get people doing things maybe in the comfort their own homes if they want.

Sally Best

Viva the urine test.

Jen Davies Oliveira

Amongst other things. Of course, you know, obviously I can do sexual and, you know, sexually transmitted infection. The ones we did, we could add it to, you know, other potential cancers dot dot dot.

Sally Best

Honestly. Thank you so much for talking with me today. And I think also thank you for sharing personal experiences. It's a lot to do. It really is. And it can bring up previous trauma and yeah, I just like I really appreciate it but I think as well, just like the work that you do is incredible, not that I’m going to affirm that in any way, but I'd just I'd love tell you what great stuff that I think you do because it is it is just incredible because it's saving lives at the end of the day. And yes, if there's that is more powerful than inclusion, you know, like there isn’t. So yeah. Thank you.

Jen Davies Oliveira

Thank you.

Stewart O’Callaghan

That’s the nicest outro I’ve ever heard. Thank you.

Jen Davies Oliveira

You know I'm not quite sure how to respond. Also thank you for your incredible podcast series. Amazing job as well.

Sally Best

Listen to season one guys. Thank you guys.

If you've been affected by anything you've heard in this episode, please see the show notes. Our list of charities and organizations that can help. One in Two was brought to you by the University of Manchester and the Manchester Cancer Research Centre. Listen to our next episode to hear from more of our researchers as they share the innovations, discoveries and projects that are changing the landscape of cancer prevention, early detection and treatment.

To find out more about what you've heard today, please see the show notes for this episode, where you'll find a transcript and links of further information and research. Cancer is one of the university's five research beacons showcasing the interdisciplinary collaborations and cross-sector partnerships that are tackling some of the biggest questions facing the planet. To hear more about Manchester's research in Advanced Materials, biotechnology, cancer, energy and global inequalities, go to Manchester dot ac dot UK forward slash beacons.

 

Sally Best

Hello. You are listening to One in Two a Manchester Cancer Research podcast brought to you by the University of Manchester and the Manchester Cancer Research Centre with one in two of us receiving a cancer diagnosis at some point in our lifetime has never been more important for our research to improve the outcomes for people affected by cancer. I am your host, Sally Best, and throughout this series I will be speaking with Manchester Cancer researchers about their innovations, discoveries and projects that are changing the landscape of early detection. With more than 52,000 men diagnosed with prostate cancer in the UK each year, there is a need for new research to improve outcomes for patients. In this episode, we speak to Professor Robert Bristow, the director of the Manchester Cancer Research Centre, Chief academic officer at the Christie NHS Foundation Trust and Professor of Cancer Studies at the University of Manchester about his research in prostate cancer. We also cover the broader cancer research environment in Manchester, the importance of teamwork and team science and research, and delivering impact through internationalisation.

Hello everybody, and welcome to this very special episode. Today we have with us the one and only Professor Robert Bristow, and it's such a pleasure to have you here. Thank you so much for coming down today.

Professor Robert Bristow

Sally. It's awesome to be here.

Sally Best

And I mean, first and foremost, how are you doing? You’re looking fab.

Professor Robert Bristow

I feel great. You know, it's a new year and and I think that, had nice holiday and yeah very invigorated for all the exciting things that are going to happen in the cancer centre and in Manchester.

Sally Best

Oh we love it. He's looking so great, guys, I have to say, because you can't see him so I get all this, you know.

Professor Robert Bristow

You can't see me blushing.

Sally Best

He's going red. But yeah, I obviously have the pleasure of working with you really closely at Manchester Cancer Research Centre. But I'm wondering if for the benefit of the listeners, you're able to tell us about what you do and describe kind of those many hats that you wear? Because there are many, they’re all different forms, different sizes. So I mean it might be a long bit of prose from you, but go for it.

Professor Robert Bristow

Well, you know, the first thing is I think the Manchester Cancer Research Centre is is an amazing place and Manchester is a fantastic place to do cancer research because first of all, many people work towards the same goals and of course we develop strategies to do that and I'll come back to that in a moment. But actually I don't think I've met a nicer crowd when it comes to kind of the team building and the execution of those teams and the impact that we can have for our patients. So I just want to say that upfront, and that's one of the reasons I came to Manchester from Canada to where, yes, as you said, a few hats. So, you know, the Manchester Cancer Research Centre is formed by three main partners, that is Cancer Research UK fantastic and world renowned charity for cancer research. The Christie NHS Foundation Trust, which is Europe's largest single site cancer centre, and the University of Manchester. You know, one of, if not the largest universities in the United Kingdom, but also has cancer as one of its beacons, which means that the university has a particular focus on cancer research. So that means then that my job as director of the cancer centre should reflect those different partners. So from a cancer research UK side within Manchester, I direct what is called the CRUK Manchester Centre and that's to translate the very best science that we have at the university and the CRUK Manchester Institute into clinical trials or devices or new inventions that benefit patients. And then I'm also leading the research domain for cancer at the University of Manchester, where I'm the University professor of cancer studies and then at the Christie I'm chief academic officer, which is really an outward facing part of the Christie again to bring the very best collaborations in not only from those partners but also national and international partnerships as well.

Now, that sounds very varied, and I suppose it is. But the challenge, but also the excitement is to pull a unified vision between those three partners through the MCRC and actually be able to be seen as a comprehensive cancer centre, not unlike large comprehensive cancer centres around the world.

Sally Best

I mean, that’s a lot and we'll get on to kind of how you balance it all. But I'm just wondering back to kind of the heart of it all and where you started. Could you tell us about this research background that led you into this amazing kind of numerous positions that you're in today and kind of like painting your days? So back to an undergraduate and going on to describe your journey into cancer research and and just, you know, how you find yourself here really.

Professor Robert Bristow

Yeah. Okay. Well, we won't take too much time, but I'm going to highlight a few of them. I mean, I grew up in Toronto, Canada, or one of the suburbs of Toronto, Canada, and I suppose I was always interested in the sciences. And when I went to university, I did an undergraduate degree actually in zoology. For a long time I thought I was going to be a marine biologist. I thought it was cool. I then found out how much it paid. I then decided to, you know, perhaps look at some other avenues and, and as part of my undergraduate thesis, I was looking at how ionising radiation actually affects cells. And that, of course, has a translational component because we use ionising radiation as part of a radio  therapy, photon radiotherapy each and every day. And these days it gets even more interesting with proton beam therapy, we might come back to that and those facilities available at Christie. But in doing so, I became really interested in normal cells and mutated cells. And of course the latter are very close to the beginning of cancer cells. And when I was making a decision to do graduate work after my undergraduate in zoology, I went to the Ontario Cancer Institute because there was someone there who was working on tumour biology, kind of quantitative tumour biology, and trying to understand the tumour microenvironment in addition to the genetic mutations. And I found that to be really, really cool. So I actually did the masters and then during one of the days, one of my mentors was actually clinician scientist, a guy named Dr. Ian Tannock, who is world renowned for the work he does and prostate cancer. And he said, Would you like to come to a clinic and actually see patients? Because it might reflect a little bit on how you're thinking about, you know, your science. And at the time, and this was the Duran Duran days, I had a, you know, a blue tail for my hair wearing kind of Peter Pan getaway pants, you know, things like that. And it was it was you know, I clearly didn't fit immediately into the clinic, but, you know, I put a tie on, etc.. And I must admit I loved it because the decision making that was happening and the way that he particularly thought about cancer in his patients, it wasn't kind of a management tree. He was actually thinking about the biology, thinking about resistance at the time, and that became a very exciting prospect that perhaps one might marry medicine and science together. And so in fact, then I applied for a medical school and it was during medical school that I had the opportunity to go to Harvard at Mass General and to do a summer project there to do the same at MD Anderson Cancer Centre in Houston, Texas, and then also at the Mayo Clinic, and also to do some actually more clinical research there. And these were really exciting times for me as a medical student because allowed me to carry on my research, but also allowed me to see the way that perhaps cancer research was practised around the world. And also, let's be honest, you know, these are great cities to live in, you know, as an undergrad. So so for me, all of a sudden it became a career in which I could see myself going into oncology, which I did, and at the same time also having a viable research practice.

And those are long days. And, you know, sometimes they have tension with each other in terms of both professional and personal life. But to me, it just seemed like a natural mix for me. And that just became more and more evident as I did more of these undergraduate travels during them, during my medical school career. And then I went into radiation oncology at the University of Toronto as a speciality. And after that I did a postdoctoral fellowship at Erasmus University in Rotterdam in the Netherlands, really focusing now down on back to really the mutation days, how mutations are repaired by cells. So the whole realm of DNA repair, DNA damage and one of the best places in the world was in Rotterdam. And so again, I had this wonderful personal experience to be living in the Netherlands for two years. But even more important, I started to develop my own ideas and really go back and forth with some very top scientists, and I carry that into my first grant and my first position back in Toronto at the Princess Margaret Cancer Centre, now practising as a genitourinary oncologist. So really focusing on prostate, bladder, kidney and testis cancer and at the same time developing my lab, but bringing these new ideas, you know, from the Netherlands into Canada and writing that first grant since it was a really, really exciting time, I'll date myself. That was 1999.

Sally Best

He doesn't look as old as all this. I promise. And also I need pictures of this hairstyle from back in the day.

Professor Robert Bristow

Right.

Sally Best

The blue. The blue. What was it? The blue ponytail.

Professor Robert Bristow

Yeah. You won't have pictures of that. I can guarantee it. No. Nor will I provide them.

Sally Best

Or else I’ll have to use my imagination. So this episode is focusing specifically on prostate cancer research and Manchester and say, my first question would be why and how did you focus specifically in on this prostate cancer research?

Professor Robert Bristow

Yeah, so it did start in in Toronto, as I hinted, and that's because I had fantastic clinical mentors who said, you know, if you at the time want to have a balance between cancer research and clinical practice, you need to choose a site in which, at least at a large cancer centre, there are multiple people who are doing that clinical site so you can fit in as a clinician scientist because you're not going to be seeing all the patients that they're going to be seeing and they actually invite you really to be a part of the group and look forward to the science that comes from it. And so the GU group or the prostate cancer group actually invited me to be a part of, you know, their clinical practice. But also the onus was on me to actually bring translational aspects of my research into the clinic. And so I think it just was a fantastic time in Toronto building the story around how prostate cancer cells spread through the body, how they become aggressive in the local sense within the prostate gland. And then I had this extraordinary experience, an opportunity to be part of something called the International Cancer Genome Consortium, which was a 20 million Canadian dollar project to sequence the whole genomes of 500 prostate cancers and understand the secrets of which cancers are aggressive, and which cancers are not aggressive, really with the down the line of sight to say for those aggressive cancers, let's provide an intensification, let's provide something more than just surgery or radiotherapy that patients were getting at the time. And for those patients that had actually cancers that were much less aggressive, maybe we don't need to treat them at all, we can just watch them. And so this is called active surveillance these days, but you need to know the differences between the two. And it all seemed to be at the time focussed in on the different genes that were activated within one patient's tumour versus another. And you really get a sense of the fact that, you know, that heterogeneity or differences between patients occur in patients who under the microscope, their tumour looks exactly the same. And as a clinician, I think one of the most sobering things that happens to you, particularly in prostate cancer where there's a big  long natural history is around four or five years into your practice and when you first start, you start to see patients failing therapy and not doing well. And yet you gave them exactly the, the best precision radiotherapy treatment that you could. And someone comes into the room and now they're failing treatment or their disease is spreading and the next person had exactly the same pathology, same clinical characteristics is doing just fine. So for me that clinical connection, why does one patient have a different response versus the other? We're starting to link them to the genetics that we were discovering, and that is something that really brought forth a lot of fruit with respect to international, frankly, accolades and branding for a program. Because in 2011 we hadn't sequenced one prostate cancer, and by 2017 we had done close to 600. And we're the leading, you know, the leading program. And the reason for that and this is something that's kind of a reason that within the Manchester Cancer Research Centre, as we build a team and it was a 70 member team and you had to have pathologists, clinicians like myself, basic biologists, geneticists, people who did whole genome sequencing, the whole technical team. And it was the whole day, I mean the whole era, I should say, of, of, of sequencing these tumours at an international level in which there were 53 projects and we were one of them. So also it was exciting to go and learn about the genetic mutations that were being discovered in other tumours. And so it was a really exciting time I think, for discovery in prostate cancer and understanding again about those aggressive versus not aggressive cancers and coming to Manchester then kind of transporting that information because these are now big databases that you can always mine actually for the rest of your life if you want afforded now a chance to think about, well, can I marry my interest in the tumour microenvironment and kind of low oxygen hypoxia that started my career along with the genetics and what's the interlock action between the two? And that's what I focussed on since coming to Manchester.

Sally Best

And there's a lot of things that you've touched on that that we're going to kind of come back to like the International Genome Consortium and hypoxia and things. But I'm just wondering if we could kind of take a step back again, tell the audience about the scale of the need of prostate cancer. So looking at outcomes and the incidence and the prognosis and things like that.

Professor Robert Bristow

Yeah, So, so I mean, the reality is, is close to 50,000 men will die of prostate cancer in the United Kingdom this year. And that's an extraordinary amount, you know, of death. And and it's the, you know, the number one non skin cancer cancer in men and and we know that there's probably a risk somewhere in the order of one in six men will develop prostate cancer. But the issue is that there will be a varied aggressivity from one person to another when we talk about those one in six statistics or so. So it's really those 50,000 men that had we understood their disease, we may have been able to reduce that number, improve cure rates. If, again, we understand that genetics at a very early stage because all of those men are dying of metastatic disease, they're all dying because they fail their primary and secondary therapies. And so if we understand aggression right up front, then perhaps again we can prevent that resistance and and change some of those deaths into cures. It's an exciting area because I think that, you know, the biology around prostate cancer, which is really a hormone driven cancer, it's a cancer driven by testosterone in the man. And so many drugs either are originally designed to stop the production of testosterone or block the action of testosterone by blocking a receptor on the cancer cell. That whole area has really changed. And from when I started it, really now where we have, you know, four or five new drugs that are really excellent, a kind of decreasing that testosterone driven kind of cancer signalling. So there's a huge amount of research in that area just focusing on how can we have better what are called hormone therapy or androgen deprivation therapies and place those into the care of patients actually much earlier on to intensify those therapies for patients who have aggressive disease? I think the other exciting thing has been really proven in the last 15 years and in some really prominent trials in United Kingdom is that some men do not need treatment when they're diagnosed. And these are patients that we have what are called low risk disease, a Gleason score six out of ten because we score out of ten, eight, nine or ten is very aggressive. A seven is in the middle and six is less aggressive. And when you follow, for example, 100 men who present with such low risk disease, only a third of them will actually progress into something that is more aggressive. So tests that define upfront which men that comes in with a low risk cancer will continue to have a low risk cancer for the rest of their lives. They should never be treated and therefore never have the side effects of treatment versus those men who are destined to fail. And again, some may fail quite quickly because the aggressivity again a really interesting area for genetics and you know and predictive assays, etc.. And of course I think men and women and anyone who has cancer these days, the expectation is to keep on hearing about personalised medicine, precision medicine. And I think we're in the era now for prostate cancer where we can start to stratify patients much better than we did before. And so the idea that we treat everybody with prostate cancer that comes to the door like we did 15 years ago is just a bygone era.

Sally Best

Yeah. And it's kind of that, you know, you'll die with it rather than from it.

Professor Robert Bristow

Yeah. Vast majority of patients. Well, that's exactly right.

Sally Best

And can we just talk about this Gleason score? What's that based on? How do you assess and risk stratify patients?

Professor Robert Bristow

Yeah, know, really good question. So. So traditionally, we would stratify patients when they come in with a diagnosis of prostate cancer and three factors. One is what we call the TNM stage. So that's tumour, nodes, the pelvic lymph nodes and also metastasis. And it's a way of saying what's the extent of the tumour. And the T category really represents whether it's a tiny lesion, you just pick up through a needle, it's microscopic or actually it's a large lethal that's actually outside the prostate affecting other areas. So that's from T one to T four is that spectrum. The second factor is the prostatatic specific antigen, the blood test, the biomarker for prostate cancer, which is something that we measure, of course, in men sometimes to look at the risk of cancer. And there's some controversies, of course, about how effective that is. But as a biomarker to follow treatment, actually it is an excellent biomarker. And so if you have a high PSA, clearly you're at higher risk because of a higher burden in your body. A lower PSA in general means a lower burden. And then there's the so-called Gleason score, which is a pathology grading score under the microscope that, again, a well experienced clinician is calling the pattern of cells. Do they look more normal or abnormal? Are they what is the ability for those cells under the microscope? What does it look like in terms of how well they're invading other structures? And that is a score actually out of five. And so you take the most prominent then the second most prominent out of five and five is bad and and zero doesn't exist anymore, as it turns out. Not for today. And then you add those two factors together. So it could be a three plus three equals six or a three plus four equals seven or a five plus five equals ten, and the last would be a tumour that has completely obliterated the prostate gland. Very, very aggressive. And again, those are the ones that really require intensification. So the difference between low intermediate and high risk localised prostate cancer is based on the spectrum of those three factors for the most part. And so if you had intermediate risk prostate cancer relative to low risk, you would have approximately a five fold increase of dying from prostate cancer. And if you had a high risk prostate cancer relative to the low risk, you have something like a 15 fold increase risk of dying of prostate cancer. So clearly in the intermediate and high risk, we tend to treat and in the high risk we tend to treat aggressively.

Sally Best

Fab and I'd like to come on to like population level genomics and different risks in terms of different populations. But I'm just wondering, so you're a world leader in prostate cancer research, but I'm just wondering, what are some of your main discoveries to date? You flagged, you know, your International Genome Consortium and things. What has granted you such an impressive and amazing title?

Professor Robert Bristow

You know, the point is there are a number of world experts in prostate cancer, and we have a number of them actually in Manchester. I think my reputation and if I can just bring it down a notch in terms of the adjectives is around the ability to think about the relative aggression of prostate cancer due to the genetic factors. So as part of a team and I really stress that and you know, one of my absolute co-investigators in the project that was the International Cancer Genome Consortium was actually at the time a young up and coming geneticist and biologist named Dr. Paul Boutros, who's now a full professor at UCLA. We still collaborate to this day, but actually we as a scientist and a clinician, came together and started again to explore the genetics of these 500 prostate cancers. As I said, I suppose what we're known about in the fundamental manuscripts and papers and studies that came out, one is that we found that prostate cancer actually doesn't tend to have a lot of mutations like changes, single base pair changes in the DNA. They tend to have what are called structural rearrangements. So additions or deletions of complete parts of chromosomes and sometimes they fused together. And so that was actually quite important because those structural changes are not always targetable by drugs. And so it's a very different cancer, for example, from breast cancer or lung cancer or other cancers. I think the other thing that we started to focus on also is that there are something called hereditary prostate cancer. And so these are cancers that are inherited, have an increased risk because of an inherited mutation in the gene. And of course people have heard about Angelina Jolie and the BRCA1 or BRCA2 breast cancer gene. Well, those genes also can put particularly BRACA2 men at risk for prostate cancer. And so we had a specific focus. Are those cancers different than what we call sporadic or kind of the I hate to say, run of the mill prostate cancer, but, you know, non hereditary. And we can talk maybe a little bit about that, you know, in a few moments. And I guess the third was that it comes back to this tumour microenvironment and genetics. And so there were two camps really in in prostate cancer biology. One was a camp that was really focussed on the genetics and so that everything is genetics and I suppose a camp that I first started in, which was actually it's about the tumour microenvironment and this word hypoxia that we've used a couple of times, which is really about stating that in tumours there are low levels of oxygen and that's because if you think of a blood vessel and as tumour cells grow, they grow away from the blood vessel. Well actually the ability for them to metabolise oxygen decreases because oxygen can't diffuse as far out. And then there are other reasons, there is abnormal perfusion opening or closing of vessels and also changes to the oxygen gradients, but we know that those cells are more aggressive based on our work using in vitro experimental studies. And then we found out in that genetic study we actually ascribed a specific signature at the RNA level to hypoxic versus non hypoxic tumours, and we found out that the hypoxic tumours were the ones that had most genetic changes. So it's a double whammy. You know, the way if you have a hypoxic tumour, you are more resistant to radiotherapy, you're more resistant to chemotherapy for different reasons. It turns out you're more likely to develop metastatic disease and, and then we found out that it was associated again with with all of these genetic changes. So we found out that if you have both hypoxia and genetic instability, if we call the genetic changes that latter term, that's much worse than having either one of them and of course, much worse than having neither of them. And the people who don't have hypoxia or genetic instability with prostate cancer do extremely well. So this ability to stratify by both the microenvironment and by genetics actually is an exciting area right now. And that's the area that we're currently involved in, in which is how does hypoxia drive genetic instability or does the genetic instability drive hypoxia due to abnormal blood vessels? It's kind of a chicken and the egg story. So you have to go back into the lab, develop models that are very germane to the genetic changes you see in prostate cancer. And we do that by using primary prostate tissues immortalising those cells and then making the changes that we see in those big genetic studies. And then we put those cells under hypoxia, low oxygen, and then we look to see what the differential changes are and we keep them under hypoxia. And what we can see is these genetic variants or mutants start to increase. So so clearly, this is an area that we need to be thinking about because if we wanted to ascribe a certain risk of a patient that is going to fail therapy or have increased metastasis upfront, then I would argue now that we have to think about both of these factors and develop a test that can basically give information in both of those realms in order to really put a patient into a category that then would lead to a specific precision therapy to target hypoxia, for example. And there are ways to do that now with some really fancy spatial omics that we might get into in a moment. So I think those are kind of the main discoveries without going into too much detail that this great team really effort had in terms of driving forward the kind of new concepts in prostate cancer biology.

Sally Best

Great. And we'll move onto current research in terms of your lab group, but the thing that's really sparked my interest is that BRCA work because I think a lot of the way that people hear about cancers is through the media. And I have personally only ever known BRCA associated with females and female diseases. So could you just tell me a bit more about that linkage of BRCA2 to prostate cancer?

Professor Robert Bristow

Yeah. So so BRCA1 and BRCA2 are of course risk factors for both breast and ovarian cancer. But it was found out that some patients who are men that carry the BRCA2 mutation are also at increased risk for prostate cancer. And comparing BRCA1 versus BRCA2, BRCA2 actually is the one that is really operational in that regard. We don't know why that's the case, because both genes or mutations in both genes are important in the other cancers. But in men it's BRCA2. And so BRCA2, for example, will increase your risk for prostate cancer somewhere in the order of 5 to 8 fold. And also it increases the aggression of the prostate cancer as well. And if you look at all series, again, these are relatively rare tumours. You know, it's about 2% of all prostate cancers are going to be in this category, but those cancers tend to be very aggressive. And the early studies suggested that, you know, 50% of men who had a BRCA2 associated prostate cancer were dead at five years. That's a very different statistic that looking at sporadic prostate cancer, taking everyone through the door and you're looking at greater than a 90% prostate cancer specific survival at five years. Right. So so clearly there was an increased aggression associated with these BRCA2 patients and so this comes back to teamwork again. But now actually an international team in which at the time and continues to be so we developed a really exciting collaboration in Melbourne at the Peter Macallum Cancer Centre and the CONFAB, a consortium that was collecting these tumours from men who had BRCA1 or BRCA2 or other types of what we call germline or bloodline mutations. And so we wrote our first paper together doing whole genomes and discovered again that the BRCA2 patients on the whole when you looked at them, their aggression was due to the fact that one they've already developed resistance mechanisms even before you start hormone therapy to hormone therapy. And the second thing is that they develop also an increased ability to spread or metastasise. So the way I can describe it is that some people, you know, may have driven a Tesla, a car, and on the Tesla, I didn't know this, but you can actually change the speed of the car on your iPhone and you can have regular sports mode. I found this out by driving in California, by the way. But there's another hidden mode called ludicrous. And ludicrous is what you sometimes see, where you see someone push down the pedal and the car just goes crazy. So when we were trying to describe BRCA2 due to the lay community, we we basically said that there are some sporadic cancers that have you know, high acceleration, those genetically unstable ones. And then there's BRCA2, which is in ludicrous mode. They have already because of the increase in genetic mutations, because BRCA2 is a DNA repair gene mutations. And DNA repair means that you're going to accumulate further mutations in the cancer. So they're already primed for resistance. And that's terrible for the patient in one way, but also because of a new category of drugs called PARP inhibitors that directly actually attack BRCA1 and BRCA2 deficient tumours. It also opens up a precision medicine approach for these patients. So something that was really aggressive, ludicrous, you know, ludicrously, so all of a sudden has a precision medicine associated with the genetic defect. And this is, you know, this is really the holy grail of oncology, is to try and link those changes, whether it's microenvironment change or whether it's mutation change to a specific new therapy that will help patients who otherwise would be, you know, down a course of having lethal disease.

Sally Best

Yeah. And I guess that yeah, that's the power of knowing the genetics of people's diseases, right.

Professor Robert Bristow

100%. And to have that information portrayed to the patient in an accurate way because of course you know everything in medicine is really an art as well as you know as well as the clinical aspects of things and and things that are part of the patient in terms of their other health, the other diseases that they have, their overall health, sometimes they're the choices of the types of further what all of this comes into, you know giving patients information that they make the best choices for themselves. But I think most patients, when they hear that there's a specific mutation that they have, first of all, it's a little bit frightening because they you know, that means that they're different than someone else. But then when you follow it up with a genuine option that says, but then this will actually attack that mutation and that's a therapy that's going to be specific to you versus 98% of men versus prostate cancer. There's great hope in that. And actually enthusiasm for going on trials that actually link those two concepts together.

Sally Best

Yeah. And I guess like prostate cancer isn't just prostate cancer. It's a massive spectrum of disease. And yeah, there's so many people that fall into different parts of that. And I think people knowing that that number one identified as not only having prostate cancer, as having a certain type that's going to respond to certain therapies, maybe it doesn't need any intervention. It's kind of it's a nice handhold, isn't it?

Professor Robert Bristow

Yeah, I think it just says that even for prostate cancer, where again, 15 years ago people might have thought that it's a relatively straightforward, you know, cancer. The reality is, to your point is that there are subpopulations of prostate cancer that need very, very different treatment and very different prognoses. You need have a different conversation with each of those patients and their families. And then you have to continue to have those conversations, of course, with patients over aggressive disease and then fail therapy. And then what's the next therapy? What's the next therapy? And again, I think that it also is one of the success stories of the last decade in prostate cancer research. Coming back to that, you know, kind of androgen receptor therapy piece where the drugs are getting better and better and better for salvaging patients who fail for therapy. And so that's providing further options. And, of course, a longer lifespan for men who, you know, 50 years ago would have died of a disease within two years.

Sally Best

Yeah, that's incredible work. So, I mean, just before we paint the picture of what you do here, specifically in Manchester, you must have been tugged between numerous cancer centres. Why here? What made you come here?

Professor Robert Bristow

Yeah, I think you're right in the sense that, you know, I was 15 years in Toronto and we were reaching the end of the five year program, International Cancer Genome Consortium. And you, you always look for challenges. And I think as long as you know, there's ability for myself innately to do strategic pieces and to bring teams together and to do novel science because of a team effort, that gets me very excited. And as I said, that that process and perhaps that success story started in Toronto and I was looking for a place that could provide a similar type of ethos and culture in which people were excited to be part of teams rather than kind of like this superstar scientist who, you know, which is who also may do fantastic work. But I'm not sure that it necessarily is going to translate to the clinic as fast. If you have a you know, when you have a larger team and have these diverse individuals that have clinicians and scientists working together and kind of go alignment and team science itself is a science, you know, there's a there's a way to build teams and to drive teams forward and to celebrate teams. And also within teams, there's an ability to recognise the experience and sometimes, frankly, scientific political savvy of, of, of the older investigator, if I can say it that way. But also there should be great room for early career investigators, you know, to do that. I think it's to take things off of their discovery and drive their own research projects and that was a very successful endpoint to the Toronto vision of what we had when we developed the team. So I was invited actually to be on a prostate cancer scientific advisory board to the Manchester's Prostate Cancer research Team. That actually was a joint project with Queen's University Belfast. So the Fast Men program was funded by Prostate Cancer UK and the Movember Foundation. And so myself and a U.S. colleague sat and gave, you know, feedback and I was quite impressed with the breadth of prostate cancer research. And then Professor Nick Jones, who at the time was the director of the MCRC, was thinking of stepping down. He'd been also the chief scientist at CRUK. So someone who certainly had a broad picture of cancer research in the UK, but also someone who could give sage advice to anyone who was interested in coming to the UK.

And he said, listen, you know, have you ever thought about coming to Manchester? And I said, No, because I hadn’t, you know, and I'd kick the tires at other places, but it's because I didn't really know all the assets. And it comes down to the fact that when you learn that the university put cancer as a beacon and a number one program, when you learned about the assets from Cancer Research UK at the institute level as well as the centre, and then when you really learnt about the Christie and how large and not only an NHS cancer hospital is, but also the, you know, ambition to be a world leading research centre, then you could, I could start to see how actually these pieces of the puzzle could be taken to the next level if there was a team science approach and if we drove that. So I actually had five visits before I accepted the job.

Sally Best

Did it rain all of them?

Professor Robert Bristow

No, it didn't. Actually. One of them was really, really hot. And actually, you know, as you know, there's not a lot of air conditioning in the United Kingdom. So so I think they did give me a fan and that's okay. I think the reason for doing that was because it was coming into a complex environment where you'd have to sew a number of things together to create that fabric of team science. And I wanted to make sure that each of the elements, the partners was willing to do that, because if they weren't, then it's going to be, you know, a false assessment, you know, in terms of whether one could achieve it. And I have to say, I've never regretted the decision to come. And I think the other thing about Manchester at the time is that it was a city that was starting to also grow in its ambition, to change, you know, even the city itself. You could see there was a buzz about it. There was something that was was changing, it was becoming more worldly. I was finding it more multicultural. You know, these are all really important aspects when when you're choosing to come to some place, because usually, you know, in Manchester, people say it rains a lot, but don't worry because, Wales is close, the Peak District is close like, you know, but you've got to live every day in Manchester. And you know, what was really telling is during the pandemic, you know, there were 78 cranes still rocking and rolling in downtown Manchester, building new economies, etcetera, because people who were coming to study come to stay. So for me Manchester City as being very exciting and then Manchester for the people I work with across those three partners have been absolutely inviting, have been really open to being part of teams. We kind of held a carrot in front of them with some town halls we might talk about, but, but actually everybody wanted to drive forward team science. And that to me was a very exciting piece because I feel in doing so and when you bring those clinicians and scientists and patients together and they co-create the projects, it's much more likely it's going to hit the patients faster.

Sally Best

Yeah, and I have to yeah, I have to say it is an amazing place to live and work. I mean, I've lived here all my life and struggle to leave and it's not like.

Professor Robert Bristow

There may be other issues there, but I agree Manchester is a great place to live.

Sally Best

But yeah fab, and I mean, what is your impression of Manchester been in comparison to other places that you've worked on?

Professor Robert Bristow

So again, I just want to be very clear the, the collaboration and the ability to, you know, to generate new ideas and those collaborations I think is one of the highest levels that I've seen before. You have to remember that at least for the places that I've worked in, these are large cancer centres, particularly in the U.S., where, you know, there are NCI comprehensive cancer centres, where there's one building, and in that building is the clinical care and all the research and the directors head of all those monies. And there's a certain core grant that is given and then it's and then the onus of course is to give great care, but also to do great research. In the United Kingdom concept of a single standing cancer centre doesn't exist, you've got to pull these elements together and depending on who controls what, some people don't like that, you know, they don't want to give up territory because it it means that they perceive that being part of a team could dilute what they're doing. But that's the whole idea of through exemplars that you show actually teams can do more rather than less. And also, I think what for me was quite exciting is that I saw some real assets in Manchester that no one else has around the world. So for example, we have a devolved health care system here that we tell people that we have an experimental health care system, they just look at you, but it's the NHS, you say it's devolved. What does that mean? It means that there's a cancer ward that basically with, you know, City council decides how the health care monies are spent on cancer and that means they can align all of the trust together with the Christie hub and spoke model. We can decide how to put genetic testing into the system. If there's a new invention, we could, for example, apply it in the Greater Manchester area to test it out and then actually reflect that back on the entire NHS. And a good example of that and you've had a podcast is Dr. Phil Crosby, who drove the lung cancer checks on a you know, on really a truck with a CT scan that went into neighbourhoods that were at highest risk for lung cancer. And that approach, you know, led to now a national, you know, a national campaign to do exactly the same thing in lung screening across the entire United Kingdom. So so that that was a challenge at first. How do you, you know, put research into devolved health care system? But it's also been very, very exciting. I think the other element, again, was the fact that the Christie has an experimental cancer medicine centre, a really strong early phase trials team, probably top three in Europe. Again, novel compounds that are coming through. I suppose the other thing about Manchester was also an interest in the basic and discovery scientists and how they could translate. And all you need is somebody to say that that's a really important aspect of their work. Not everybody may want to do that, but I think the team, the teams that we built, were really allowing some of the basic scientists to finally feel like they could translate their work. You know, and hand it over to clinicians. And so we had a series of these town halls when I first came, which was you to give a pump priming amount of money to teams in specific tumour sites, prostate, breast cancer, lung cancer, etc., and come up with a brand new idea that hadn't been thought about before, that was Mancunian. In other words, it only could be done in Manchester either because of a patient population or technology, etc. and that it might be a late headline in The Guardian in three years. You know that research was successful, and I'm very proud of those town halls because people came together and did come up with novel ideas. And I suppose it's providing that opportunity for brain time.

And in two of those the ideas came up or, you know, the ideas were bubbled up by patients. You know, the lung cancer all was really interesting because the patient said our lung cancer is different in Manchester relative to anywhere else. And I looked at my colleagues, Phil Crosbie again, and also Professor Caroline Dyer, who's driving our Lung Cancer Centre of Excellence and they didn't know. And so we looked and in fact the RAS oncogene, which is an oxygen that's very important in many tumours including lung cancer, had a mutation that was in a much higher incidence in Manchester than in other places. We didn't know why, made a mouse model of it started to really look at it targeting RAS now so that was from a patients question. And that's why it's so important how the patient in the room actually led to a completely new programme. And, and for me that's really, really exciting. And it's because there were there was something different in Manchester. Similarly in breast cancer, the breast cancer researchers, Dr. Gareth Evans and others had formulated a new test based on the germline, the bloodline of women of who is at greatest risk or not. And so the project was to go and find women in the ages of 30 to 50 who might have that signature, bring them in for state of the art mammography, and really then find those young women who are most at risk for cancer, put them on novel trials. And again, that that approach could only be done if you have a devolved health care system, could work with the GP's. But also you had this unique test in breast cancer. So, so so I think, you know, I, I don't think those town halls where you basically had to de cloak from the hospital that you're at for the programmes are already doing and actually be part of a a creative a co-creative process and the, the funders and the, you know and the comms people were not allowed to say anything at the back of the room just watching this. And in fact, in two of the town halls we actually had a reporter from The Guardian sitting in. And because what we were trying to do at the end was generate headlines, you know, and I think what she what she said was quite funny. Of course, she said it was great sessions, these are amazing as she reported on them, she said, but scientists are terrible at giving headlines. And I think that's you know, that's why we need people to, again, always make sure that we're reaching out to the lay audience in an appropriate way. But I'm very proud of those because a number of them, you know, led to a big consortium. I mean, the breast cancer led to our ability to form, you know, a five partner International Alliance for Cancer Early Detection. And and I think luck favours the prepared minds. So those town halls really got people to open their minds to think about what are the best assets in Manchester, to write more provocative grants that would be competitive because of those assets to recognise them. And then and then really to have international branding for a number of these programmes.

Sally Best

Yeah, for sure. And just to flag, we spoke to both Gareth Evans and Phil Crosbie in season one. So if you haven't go and have a listen because they’re fab. And so coming back to the research, prostate cancer research, I mean piece de resistance question, What are you and your lab doing now?

Professor Robert Bristow

Well, I think we're doing some really exciting things and in some very translational things. So my lab consisted of PhD students, postdoctoral fellows and also clinicians and training, either doing their Ph.D. or further down in their training. I mean, soon their own independent scientist. And so we focussed on those two areas again, the genetics of prostate cancer and again the tumour microenvironment type parts in that interaction. And we're also very interested also in hereditary prostate cancer. So what we're doing now is taking those those cells I described previously. So men undergo surgery for their prostate cancer, we freeze down their prostate cancer to do the fancy whole genome sequencing in actually something called spatial transcriptomics, where we can actually measure the changes in RNA expression and in spatial proteomics changes, in protein expression actually on the actual tissue sample and map that to areas that have low oxygen or high oxygen and prove or disprove the theory that genetic instability is associated again, with these with these hypoxic areas. And it's important because we can target those with a number of different drugs. So we have this kind of molecular pathology theme. We then have developed primary tumour models, tumour cell models, by taking the normal tissue of men and actually knocking out what are called tumour suppressor genes or activating oncogenes, cancer causing genes. And those are novel models from around the world. Well, for the world to access, in which again we track the changes that were placing into those cells, we look for the consequential genetic changes thereafter. And what I'm really excited about in those models is that we see a number of men with hereditary prostate cancer coming through the doors of our clinics in Manchester because we see 2000 new prostate patients per year. It's a remarkable number. Again, we're a very large cancer centre and because we are hyper vigilant about finding men who have these mutations in genes, you can infer them from the clinical factors, but sometimes actually come already with a no mutation because a relative of theirs had breast and ovarian cancer and we're BRCA1 and BRCA2. And what we do there is we again take the normal tissue of those men, we freeze down the tumours and we investigate the tumours, but we want to develop new models. So we take the normal prostate tissues of those men who already have a mutation in them. And then again we change the oncogene and the tumour suppressor genes that we see in the genetics and basically drive these new models and these are the first models that I'm aware of in primary prostate cultures that will reflect these types of hereditary changes in genes such as BRCA2. There’s another gene called ATN. And so we're very excited about trying to understand again, the relative aggression of these cells and what's the tumour microenvironment then in a bracket tumour versus a sporadic tumour and to use the latest technologies to do so I think in this might lead into some more of the questions you were hinting at the very beginning of the interview. We're also interested in men who come from African ancestry because they tend to have more aggressive cancers. They actually tend to have a higher incidence of BRCA2 in those cancers. So we are also developing models that reflect really the diverse populations of Manchester instead of just focusing on Eurocentric models.

Sally Best

And I mean, I'm just wondering, so you talked about black men then, and that's definitely leading on to my next question. Is there a stat in terms of Caucasian versus black in terms of prostate cancer incidence?

Professor Robert Bristow

Yeah. So so the incidence of prostate cancer and the relative regression of prostate cancer is increased in men with African ancestry. The data are quite clear to that the reasons behind it sometimes are complex, could be genetics. In the United States for the African-American community, there continues to be a debate as to whether or not aggression is due to differences in socioeconomic status and, you know, and the ability to access health care early. But but I, I think now we know when we've looked at African American men and their genetics and we've started to look at the genetics of men who are born and have prostate cancer in the African continent, particularly East and South Africa, we know that a number, a disproportion of those men have much more, you know, genetic mutations and structural rearrangements and these aggressive features that we see. And so that suggests that actually there's a different type of prostate cancer in men of African heritage. And the reason I say African heritage is we have to be very, very careful because, of course, in the United States then many of the men who would present the black men would be of African American heritage. In Canada, for example, there was a large Afro-Caribbean community, and that's really the patients we saw coming through the door. And I think in the United Kingdom you're seeing Afro-Caribbean, but also African continent, if I can use that, you know, and so it is very important to pull apart, you know, these different populations. They have different risks and in different, I suppose, nature versus nurture in terms of where they're actually living, environmental factors. But but on the whole, this is something that in general we really are paying attention to the differential ethnicities of people because of course, the just by definition, your bloodline is going to be different from one ethnicity to another. And we infer now, based on the whole genome sequencing studies, that also the tumours are different and that means coming back to this concept of precision medicine that we can be more precise if we start to think about ethnicity as part of that equation. I think where we're at right now is a real discovery phase and working with communities to try to understand what those genetic changes are at the present time. For example, the FDA does not allow an ethnicity specific clinical trial because there aren't enough data as far as they're concerned to support that. You give one treatment to someone who's black versus a patient who comes from a Caucasian background. But I think we have to address this in a manner that says that if we're so interested in the different genetic mutations, then we have to we you know, we have to just take the onus on ourselves with the communities that those mutations might affect.

Number one, how tumours respond to the current therapies, and number two, how they how that information might generate new treatments and three, how the bloodline may actually change side effects of treatments. And that's a better conversation with the patient. We can do that.

Sally Best

And I guess it's one of those things that there must have been a lot of breeding of health inequality because I mean, particularly in this country, correct me if I'm wrong, but clinical trial uptake is mainly kind of white Caucasian. And so then you have that differential between the white Caucasian and the black men. And if they're not represented in the research, then you breed that health inequality because the treatment isn't tailored to them. So this work is really, really important in terms of, you know, streamlining and getting that precision medicine tool. I'm just wondering kind of specific to Manchester, if we have any ongoing international collaborations that are looking at that side of things.

Professor Robert Bristow

One of the best recruits, I think that that I have had as a director of the MCRC was to bring in Professor David Wedge from Oxford, who's a world renowned cancer geneticist and has a real interest in prostate oesophageal and other cancers, particularly in prostate cancer, has collaborations. You know, looking at the differential spectrum of cancer in African continent men and and we also have a more broader collaboration with Kenya, particularly university teaching research and referral hospital that's aligned to the Christie in which we're looking at a number of tumours in African continent individuals both in men and women and looking at those ethnicity differences and tracking how they're responding to the therapies on their end relative to how our patients are doing. And I think that's a really good backboard to go back and forth and to understand what are the best treatments, because we'd like to use the exemplar of our work with Kenya. And that's very, very important. We're co-creating this work based on their needs because those those ancestries are also patients coming through the door at the Chrisite and so so engaging the black community in Manchester which we're starting to do now in terms of understanding about the genetics, both bloodline as well as to work and to have them say, excuse me, that actually, yes, we're really interested in these differences because we do believe it's going to be important and we do want to be part of clinical trials, novel clinical trials that address these issues. That's a really important voice for the health care system to hear, for the government to hear and for us to hear. As you know, as as oncologists. So so to me, it's a very, very exciting area. I think it used to be a very sensitive area because, you know, any time there's ethnicity, you know, people start to think about solely differences, potentially socioeconomic, all of these issues, which are very complex issues that I can't solve. But what I can do is say to somebody, how can I help you understand further about what is your disease? And then you are going to help me in providing better treatment for you and your loved ones down the road and I think one of the things that we have heard from the black community, if we just focus that on in Manchester, is a some somewhat of a distrust about the genetics. And so and we heard this through our community leaders, you know, who've been very helpful for us to, you know, to see how to address kind of an education piece, how to understand what are concerns of the community so that we can better provide them with information that would suggest that they would be excited about joining clinical trials. And sometimes, you know, words are around the relative security of genetic data. Where does it finally wind up? Does that wind up in the police as a wind up in insurance? And you have to convey, again, that just won't happen. But I can understand that someone would be concerned about that. The second is, again, about, you know, again, the kind of the things we used to call the guinea pigs in clinical trials. And, you know, and yet I would say for communities that have specific genetic changes, it's exactly what you want to get involved in because that's only way that we can know, you know, who will respond and who won’t respond. So it's a very exciting time, I think, for Manchester to be reaching out in terms of internationalisation to different countries to understand those changes because they reflect back on the diaspora that we have here and frankly in the entire United Kingdom.

Sally Best

Yeah, Yeah. And we have a very diverse population here indeed, in order to serve them, we need these international collaborations. So I mean, my next question would be is do you see that as the future of cancer research that globalisation aspect that's kind of not only focusing on the populations here and translating through to London and things, but is it is it more kind of far reaching populations that are across the seas?

Professor Robert Bristow

And yeah, I personally think that's the way that I would like to see Manchester growing is again a global you know, a solution provider for countries that have these different, you know, genetic changes and coming up with solutions in their health care systems to address those. I think what's important to recognise is that, you know, team science, as we said before, can occur at a number of different levels local, national and international. And therefore, you know, Manchester won't do this by themselves. And I'll bring up the example of, you know, early detection. The grant that we currently have with Kenya is funded by the NIHR. So the National Institute for Health Research to focus on the early detection of oesophageal cancer in Kenya, and that's with mobile endoscopy units going to different counties that actually don't usually have the resources to have fancy health care institutions locally and actually, you know, load up not only the pictures of the oesophagus at the time they do the endoscopy, but also biopsies and all that information is digitised and sent to a central hub, really trying to connect these relatively poor counties with the relatively rich areas of Nairobi that have access to these health care systems. So that provides a framework in which that team aspect is between two countries, the UK and Kenya. But actually there'll be a number of people who are really interested in genetics of oesophageal cancer in Kenyans and early disease versus late disease across different countries. And we already know that there's an interest in that. So I can only see that that is going to increase in terms of the team that is involved in in the early detection in Africa and who will be collaborating with and and the natural collaborators right now are part of the Alliance for Cancer Early Detection, of which the other partners are.

The university are Cambridge University, UCL, Stanford and Oregon State University, in which together we're starting to think about exactly what you just said. What are the early detection needs in different countries, And that is going to have a huge impact in terms of the number of people that we can potentially change their course of disease if we can find cancers earlier. So so the idea that you get, you know, higher and higher levels of kind of state of the art technologies in assays within, you know, what we'll call the first world or the in the Western hemisphere, that's all well and good and of course there's a profit issue to that and a number of different aspects. The question comes from an altruistic and global standpoint is which of those elements can you transfer into other countries in collaboration and co-creation, and how do you do that? And how does it fit into the health care system? And so that broadens, you know, an entire area of applied health research from the University of Manchester. And we've brought those people now into the cancer realm. So I'm excited for the Manchester Cancer Research Centre because I think that's what we do. You know, we do reach out to other faculties, we do reach out to other researchers and bring them into the cancers so they can ask their questions in really exciting environments and such as Kenya. But absolutely, we'd like to do the same thing. For example, in Singapore and in Malaysia and in South America and in India. And there are efforts ongoing in those particular areas. And you've got to pick and choose the projects because I think perhaps in the past people have tried to be too broad and do everything. And by focusing down on one question again, coming back to that team science, having the members of another countries, you know, scientific team working with you to that goal and then achieving it and achieving it with a sense of an understanding both sides about what the important elements are. And that community piece that I think is the exemplar. Then for the next project, in the next project, the next project, as opposed to say, you're going to do early detection of all cancers in Africa. I mean, it's, you know, you got to chew these little bits and see what works and doesn't work with the different systems and learn from each other. That to me is one of the exciting aspects of the internationalisation program.

Sally Best

And we have yeah, it's incredible. And I think it's shared learnings and it's not only benefiting, you know, populations across the globe, it's also the return shared knowledge for populations here. And that's the real important thing. Like we're a beautiful country because we are incredibly diverse and in order to serve our population, we need to serve every single person there, not just the kind of white Caucasian cohort.

Professor Robert Bristow

Well, that's exactly right. And I and I just want to also say something that is, you know, it's an embarrassing statistic, and particularly for someone like myself that was involved, the international, you know, Cancer Genomics Consortium. But the reality is, is when you look at the world's repository of whole genomes for cancer and you look in Africa is a good example where, you know, Africa, 16 to 20% of the world's population, depending on how you define it. And you look at the genomes, 97% of the hundreds of thousands of genomes that we actually have to explore, etc., are Eurocentric, Caucasian. Yeah. And less than, you know, less than 2% are African. And that number needs to change. So scientists need to recognise that they're biasing their results and in their research, if they only focussed on it, drug companies need to recognise that if they only focus on Eurocentric that again they're missing important mutations, then where drug development and potentially novel clinical can occur. And I think that internationalisation and this approach to really making up for the last 20 years where we've really focussed on Caucasian populations is really the next era and it's the next arrow precision.

Sally Best

Yeah, incredible. And just on that note, what is your vision for the future of prostate cancer research here in Manchester?

Professor Robert Bristow

So I think the first thing that we want to do is to really, I would say, focus on those hereditary syndromes and actually provide some unique treatment choices for men that come in with different mutations. So part of that is to develop a program in which maybe all men might be sequenced with their tumours so that we can understand what to do for each individual man who comes through the door. And because of that, we'll start to pick up these DNA repair mutations in 3% of those 2000 men that come through. But we also know that men who become resistant to therapy actually also develop a BRAC like tumour, even though they didn't have BRAC in their germline. And there are ways to test for that and they should go on to novel therapies as well. So a very exciting way to triage patients with localised disease and metastatic disease to two new clinical trials. The second piece is comes back to early detection of aggressive prostate cancers. And if we could just think of a maybe in ten years, where would I like to see the crystal ball and where I'd love to be is back to that concept of those patients who come in with low risk cancers, of which a third are going to progress, wouldn't it be nice not only to know the third that progressed, but actually because you've caught them early and understand the genetic changes that actually you have a drug that prevents them from going further, it stops them in the tracks and you then stop that third from going on to have the side effects of surgery or the side effects of radiotherapy because you understand the biology of the disease and use a drug to offset that which is different than hormone therapy. It might be a drug that is much more about stabilising the genetics and or getting rid of mutants when they occur. But that to me would be a really exciting area and that's something that also we're working on. And I think the other piece that we'll continue to focus on is, is to get some novel clinical trials with hypoxia targeted agents we know for head and neck and bladder cancer that hypoxic tumours are more aggressive and if you use anti hypoxia therapies, those patients will benefit. Some might be drugs, other might just be actually during radiotherapy breathing in an agent that increases the oxygenation to the tumour at the time of radiotherapy. But it could also be a tablet. And so there are companies who are very interested working with us to say, okay, what's the test, you know, Rob Bristow and team that says a patient has an aggressive hypoxic tumour? As I said, that needs to factor in the genetics and the hypoxia and then let's put those patients on specific trial which compares standard therapy to the novel drug, then really change things up for those patients going forward, because I do think those are the patients that are going to develop metastasis and fail, you know, current therapies quite rapidly. So I think those are the three areas, the hereditary, the early early detection, prevent and preventing further progression and then the tumour microenvironment actually having trials for prostate cancer that make a difference to patients by targeting those aggressive features. I can see Manchester having an impact in those areas.

Sally Best

I mean, it sounds like an amazing future and I for one am very, very excited to see what comes to fruition from this because it's just it's constant, kind of amazing research and publications that are coming out from the teams here. So I'm going to come on to my final question then. It's a bit of a personal one, but I like to ask everybody and it's that question of I mean, how does it feel personally to know that you're working to benefit the lives of these people that have been diagnosed with kind of cancers?

Professor Robert Bristow

Well, first of all, it's a gift, actually, to be able to work in that in that kind of team environment. And again, I keep on using that four letter word team because there's no way that you can do it on your own. If there's one thing that I learned as a busy clinician, you know, in Toronto is that that all the other clinicians that were working in clinics on other days or right beside me, we all had one thing in common that's to give the very, very best care to try and cure those that are curable and for those that have incurable disease to make their life as best as possible for the time that they had. And it's a very simple concept, isn't it? And that's a partnership with the patients. So so for me, it's the ability to give more accurate information to the patient and their family, which provides more options than we've ever had before for their treatment. And then they get to decide, you know, because of a number of issues, lifestyle, other disease, etc., what is best for them. Yeah, that's great health care. And I and I kind of think about it's almost like the you could think of it as the Expedia of health care, you know, like Expedia. You going look, you know, you know where your destination is. But there are a number of different routes. One could be non stop, one could be have a couple of stops, different prices, you know, different side effects, quote unquote. And and you can imagine if we could be that precise and give patients, you know, if you fail this, then we'll neatly go to that, etc., that they can see they have hope, even under the duress of aggressive disease, that there's going to be something else and something else. And I think we're getting to the point where we can have those conversations. So to me, that's a very exciting time. It requires people who are driving the basic and discovery biology of prostate cancer. It requires those people who are interested in the biomarkers of prostate cancer. It requires interactions with big pharma in terms of having drugs and immunotherapies available for them. Those novel clinical trials and those clinicians at the Christie and elsewhere who are part of experimental cancer medicine teams and are trying to drive that into, you know, into the health care system as quickly as possible. And then success there, of course, makes it available to the rest of the United Kingdom, you know, as it goes through, again, NICE guidelines, etc.. So it's always a long road, you know, from discovery through to the patient. But when you've got the team and you've got the conduit, it's a faster process. And I think patients expect that. The days.

Sally Best

And I mean what better place to facilitate that your team here is incredible. I love the acronym together everyone achieves more.

Professor Robert Bristow

Yeah agreed well done.

Sally Best

But I mean we could go on to say much more that I'd love to talk to you about, but I know your diary is very busy, and honestly, thank you so much for speaking to us for an hour. Like, it's incredible. I know it's exhausting, but we need to hear it, you know, from the one and only Rob Bristow.

Professor Robert Bristow

Oh, that's that's really that's really kind, Sally. I mean, your enthusiasm just went like that. But but again, you know, Manchester is a place for teams, whether that's in football or whether that's in cancer. And and to really, you know, be successful, we need to keep on driving that type of culture. And that's what's going to win the war on cancer, not only locally but also internationally. So it's a great place to be.

Sally Best

Well, thank you so much. I have you have a fab weekend.

Professor Robert Bristow

I'm going have a great weekend. And this is a great start.

Sally Best

Thank you. Thank you so much, guys. I'll put show notes into any more information that you need and want to know about Rob Bristow, his team and all the collabs that we've mentioned. But yeah, thanks for listening again to this very special episode. Bye.

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