Key Considerations for Detecting and Targeting BRAF Mutations - Episode 12

BRAF Mutations in Colorectal Cancer


John L. Marshall, MD: We have recognized over the last couple of years that there is a subtype of colon cancer that has a BRAF V600E mutation. This is the same mutation that we see in melanoma and other cancers. It is a driving mutation for colorectal cancer, but to target it we have to go at it in a different way. So we’ve spent the last few years figuring that out.

If you find a BRAF mutation in your patient, you already know that’s probably a bad prognostic sign. They tend to be more common on the right side of the colon cancer, but they can occur anywhere within the colon. There is more than 1 BRAF mutation, and what we’re really talking about here is just the V600E mutation. We don’t really know what to do with the other BRAF mutations yet.

So it’s important to find it. You want to know about it to use it as a prognostic marker for your patient, but now you also need to know about it because it is a therapeutic target. We’re not quite where we were with HER2 and breast cancer. We all remember that, at the beginning, having HER2-positive breast cancer was a bad thing until we figured out how to target it, right? And so, with BRAF we know it’s a bad prognostic thing, but we are increasingly figuring out how to target it. That doesn’t mean you’re rooting to have a BRAF mutation, but it is less of a bad thing because we have ways to deal with it.

If you have microsatellite unstable colon cancer, you have lots of genetic abnormalities, 1 of which is commonly this BRAF V600E mutation. There can also be BRCA mutations and others like that in MSI [microsatellite instability]-high colon cancers. And for us in the colon cancer world, we have to figure out how to prioritize those mutations. Would an MSI-high colon cancer push us more toward immunotherapy? Or would the BRAF-mutated colon cancer push us more toward a targeted therapy approach? I think the consensus at the moment is, in fact, to try for the immunotherapy approach first. But it’s sort of a wealth of riches when you have both of these targets in these patients.

Transcript Edited for Clarity