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.
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.”
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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.