Scientists find way to target cells resistant to chemotherapy

Scientists from The University of Manchester have identified a way to sensitise cancer cells to chemotherapy - making them more open to treatment.

The study published today in Cell Reports, could pave the way for the development of drugs to target cells that have become resistant to treatment.

The research team made the discovery whilst exploring the possible mechanisms behind resistance to chemotherapy drugs like Paclitaxel, often used to treat breast and colon cancer.

Dr Andrew Gilmore, who led the research team at The University of Manchester, is part of both the Wellcome Trust Centre for Cell-Matrix Research and also the Manchester Cancer Research Centre.

He said: “Cells replicate and divide through a process known as mitosis. This process is carefully controlled and if any mistake is made during normal division then the cell undergoes apoptosis – otherwise known as controlled cell death.

“Failure of cells to complete mitosis correctly can be the start of cancer. We wanted to understand how this failure – delay of cell division - activates apoptosis, and why some cancer cells may be able to avoid being killed.”

Cancer cells replicate rapidly, and chemotherapy drugs such as paclitaxel target mitosis as a way to kill these quickly dividing cells. But cancer cells can develop resistance to the drugs.

The researchers found a particular protein known as ‘Bid’ in colon cancer cells, and looked at what happened when Bid was switched on.

Their results show that Bid is turned on as cells prepare to divide. This primes the cells to die if cell division takes too long. Cancer cells that were resistant to chemotherapy still turned Bid on, but went through mitosis too quickly for it to kill the cell. However, these resistant cells could be made to die by directly targeting the part of the cell where Bid works.

“Our findings demonstrate that Bid plays a central role in mitosis-related cell death.  This opens up new areas of research into drugs that might be able to kill cancer cells that have become resistant to chemotherapy. This could eventually be of huge benefit in a clinical setting and help patients who suffer from advanced stages of colon cancer,” added Dr Gilmore.

Notes for editors

For media enquiries contact Kath Paddison, University of Manchester Press Office +44(0)161 275 2111 or kath.paddison@manchester.ac.uk

The paper entitled ‘Phosphorylation of the Proapoptotic BH3-Only Protein Bid Primes Mitochondria for Apoptosis during Mitotic Arrest’ by Pengbo Wang, Jennefer Lindsay, Thomas W. Owens, Ewa J. Mularczyk, Stacey Warwood,Fiona Foster, Charles H. Streuli, Keith Brennan and Andrew P. Gilmore is available upon request.

The University of Manchester is part of Manchester Cancer Research Centre a three-way partnership also including Cancer Research UK and The Christie NHS Foundation Trust. Andrew Gilmore is also a member of the Wellcome Trust Centre for Cell-Matrix Research.

About colon cancer:

• Bowel cancer is also called colorectal cancer and includes large bowel cancer (colon cancer) and cancer of the back passage (rectal cancer or cancer of the rectum).
• Bowel cancer is the fourth most common cancer in the UK.
• More than 8 in 10 bowel cancer cases occur in people aged 60 and over.
• Although death rates from bowel cancer have been falling since the 1970s, it remains the second most common cause of cancer death in the UK after lung cancer.
• For more information - http://publications.cancerresearchuk.org/downloads/Product/CS_KF_BOWEL.pdf

• Breast cancer is the most common cancer in the UK.
• The lifetime risk of being diagnosed with breast cancer is 1 in 8 for women in the UK.
• Female breast cancer incidence rates in Great Britain have increased by 72% since the mid-1970s
• For more information - http://publications.cancerresearchuk.org/downloads/Product/CS_KF_BREAST.pdf