Two-Pronged Approach Brings Hope for Bowel Cancer Treatment
1 March 2011 – ICR 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.
The team 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.
This approach of blocking two pathways at once is known as synthetic lethality, which was first pioneered in cancer by the ICR’s Professor Alan Ashworth and is already used in a number of cancer drugs under development.
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 and other cancers.
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.
