Cancer Research UK scientists have discovered how two genes – called MEK and MET – cause bowel cancer cells to become resistant to treatments used against the disease, according to research in the journal Cell Reports*.
“Our discoveries in this deadly disease have identified an exciting new route to treat cancer patients.” – Professor Patrick Johnston, study author. The team at Queen’s University Belfast, are now testing a new approach to targeting MEK and MET in a clinical trial**.
The two proteins were uncovered when the researchers looked at all the different pathways and interactions taking place in bowel cancers that have faults in the KRAS gene. Around 45 per cent of bowel cancers have this fault.
They found that these bowel cancers switch on a survival mechanism when they are treated with drugs that target faulty MEK genes. But when the researchers added drugs that also block the MET gene, the bowel cancer cells died.
Study author, Dr Sandra van Schaeybroeck, a Cancer Research UK clinician scientist at the Centre for Cancer Research and Cell Biology at Queen’s University Belfast and consultant oncologist at the Belfast Health and Social Care Trust, said: “We’ve discovered how two key genes contribute to aggressive bowel cancer. Understanding how they are involved in development of the disease has also primed the development of a potential new treatment approach for this disease.”
Each year around 41,000 people are diagnosed with bowel cancer in the UK and more than 50 per cent will develop an aggressive form of the disease that does not respond to standard drug treatments. For this group survival is less than five per cent.
Professor Patrick Johnston, Vice Chancellor of Queen’s University Belfast and senior study author of this study, said: “Understanding the genes that cause bowel cancer is a key focus of our research. Our discoveries in this deadly disease have identified an exciting new route to treat cancer patients.”
Professor David Waugh, Director of the Centre for Cancer Research and Cell Biology, said: “The publication of this research by Dr van Schaeybroeck and her team demonstrates our commitment to performing excellent science here in Belfast that can be directly translated to the clinic.”
Nell Barrie, senior science information manager at Cancer Research UK, said: “Finding new ways to treat aggressive bowel cancers is vitally important to help more people beat the disease. We look forward to seeing the results of clinical trials that use a ‘double-hit’ approach to overcome drug resistance.”
*Van Schaybroek et al. ADAM17-Dependent c-MET-STAT3 Signaling Mediates Resistance to MEK Inhibitors in KRAS Mutant Colorectal Cancer (2014) Cell Reports. doi: 10.1016/j.celrep.2014.05.032
**The MErCuRIC clinical trial is supported with 6M euro grant by the European Commission to a European Consortium led by Queen’s University Belfast. This clinical trial will deliver personalised medicine to Northern Irish patients and patients from other European countries. Overall, this pan European collaborative effort involving 13 research/clinical teams from 9 European countries.