Personalized Medicine In Metastatic Colon Cancer

Progress in the treatment of metastatic colorectal cancer in terms of personalized medicine, has been slow. We know a couple of markers that tell us what not to use, and now more recently, one that we know is proactive and tells us what to use. In terms of how it fits, for the longest time, KRAS at codons 12 and 13 and now what are called all-RAS, or NRAS, are a series of different mutations in the RAS gene. These are all biomarkers that largely tell us which patients are very unlikely to benefit from the EGFR antibodies. They give us some prognostic information as well. So, those are two biomarkers that tell us what not to use.The BRAF mutation is an important biomarker, which we now understand to be a particularly negative factor. This is something that should guide us to treat patients differently than standard, because patients on average do poorly if they’re treated with standard therapy with a BRAF mutation. BRAF mutations do not exist in patients with RAS mutations. MSI-High, the so-called microsatellite instability, is a marker of a genetic predisposition to cancer, a familial cancer risk gene that has some bearing in stage 2 colon cancer. But in terms of metastatic colorectal cancer, its importance relates to the use of checkpoint inhibitors. In metastatic colorectal cancer, about 3% of patients with metastases are what’s called MSI-High. Those patients have a reasonably good chance of benefiting from the checkpoint inhibitors.