Dr Alan Venook Outlines the Challenges of Right-Sided Colon Cancer

Sidedness matters for metastatic disease, and right-sided colon cancer has been known for a shorter time than left-sided colon cancer, making the right-sided version more difficult to treat, explained Alan Venook, MD, of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Why is right-sided colon cancer such a challenging disease to treat compared with left-sided disease?
First of all, we’ve only known about this for a little while. We should have known about it a long time ago; but it turns out that the sidedness matters for metastatic disease, not for stage 1, 2, or 3, at least the best we can tell. It may be that the right side is just a different disease because it comes from a different part of the embryo. The right colon comes from the mid gut, the left colon from the hind gut, and the transverse colon is where they merge in embryogenesis. There may be some mild molecular differences, a tendency for BRAC mutations to be on the right side. Our working hypothesis right now is more that it’s got to do with its biome, the microbiome which may either impact the biology of the cancer or the impact of the immune system on the cancer. So, we’re not exactly sure but we think the biome may be responsible.

Some of this is fed by the recent observations—the amazing observations that you can find bacterial DNA in tumor metastases. Let’s say you take a biopsy of a patient with liver metastases. When we do next [generation] sequencing looking for the genetic mutations, we throw away a lot of DNA which doesn’t make sense. Turns out, some of that may be bacterial DNA, and what is that doing there and if it’s there, is it there for a reason? We see it in colon cancer liver metastases, we see it in colon cancer liver metastases, we see it in pancreas cancer liver metastases—maybe we’d see it everywhere if we looked. That’s the mystery. I think that’s the most exciting thing in terms of the challenge of figuring out just what the biome is and what we can do about it, but that may account for the sidedness.     
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