Tuesday 1 March 2011
Cancer Research UK-funded scientists have discovered that blocking two cell DNA repair routes at once could provide a completely new way to treat bowel cancer and potentially other cancers, according to research published in Cancer Research, today (Tuesday).
The team at The Institute of Cancer Research (ICR) blocked the action of a protein called PINK1 in bowel cancer cells in the laboratory. PINK1 helps protect cells from DNA damage and blocking it caused an increase in DNA damage.
In healthy cells, this is repaired by proteins called MLH1 or MSH2 – which fix DNA damage. But cancer cells often have faults in MLH1 or MSH2 and cannot repair these faults. The accumulative effect of losing both the PINK1 and MLH1 and MSH2 proteins causes DNA mistakes to build up to the point where the cancer cell dies.
Faulty genes including MSH1 and MLH2, are found in the inherited condition Lynch Syndrome** as well as non-inherited forms of bowel cancer. People with Lynch Syndrome have a significantly increased chance of developing bowel cancer. They also have increased risk of developing stomach, endometrial, ovarian, kidney and other cancers.
Co-lead author, Dr Christopher Lord from the Breakthrough Breast Cancer Research Centre at the ICR, said: “There have been major advances in the treatment of bowel cancer but there is more work to be done and we are searching for new treatments to increase survival from the disease. Our ultimate aim is to develop drugs which kill bowel cancer cells without damaging healthy cells. This research shows us that this is possible and helps us focus further research to develop more effective ways to treat this disease.”
Targeting PINK1 is not currently possible in patients. But developing drugs that can mimic these effects could provide new ways to treat bowel cancer patients who have faulty MLH1 or MSH2 genes.
The research suggests that targeting genes in the mitochondria is also a potential way to treat cancer.
Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “Most standard chemotherapies kill dividing cells, which harms both healthy and cancer cells, causing side effects. But this research reveals that it is possible to hone in on and destroy tumours - with little damage to healthy tissue - by simultaneously blocking two survival techniques used by cancer cells.
“An experimental drug called PARP, which blocks two DNA repair routes at the same time, is already in clinical trials as a potential new treatment for inherited breast and ovarian cancer. This research suggests that similar techniques could be used to treat other cancers.”
-ENDS-
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Notes to editors:
*Martin S.A., Hewish, M et al. Parallel high throughput RNA interference screens identify PINK1 as a potential therapeutic target for the treatment of DNA mismatch repair deficient cancers.
**Also called Hereditary Nonpolyposis Colon Cancer.
The Institute of Cancer Research (ICR)
- The ICR is Europe’s leading cancer research centre
- The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research Assessment Exercise
- The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe
- The ICR has charitable status and relies on voluntary income, spending 90 pence in every pound of total income directly on research
- As a college of the University of London, the ICR also provides postgraduate higher education of international distinction
- Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world
- The ICR is home to the world’s leading academic cancer drug development team. Several important anti-cancer drugs used worldwide were synthesised at the ICR and it has discovered an average of two preclinical candidates each year over the past five years
For more information visit www.icr.ac.uk
About Cancer Research UK
- Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research
- The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last forty years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.
For further information about Cancer Research UK's work or to find out how to support the charity, please call 020 7121 6699 or visit www.cancerresearchuk.org