DR VENOOK: It’s a group that’s using next-generation sequencing to look at candidate genes that are potentially targets for therapy in cancer.
I think their platform is they look at 188 genes today. They may look at 200 tomorrow. I mean, it’s a mobile platform and they can add and subtract genes of interest.
DR LOVE: And I guess the other thing, because they had data that was in lung cancer presented, in breast cancer, was that they can do it on paraffin tissue and not that much tissue.
DR VENOOK: They can, in fact. The technology is evolving so that each group is leapfrogging beyond the next. And it is remarkable what they can learn from a small section. This particular paper, I think, is…the word that I object to is “actionable” in the title, which is that, in fact, they did find a whole host of mutations and a variety of perturbations of genes, but whether they’re actionable in colon cancer is a different question. Because, for example, they did find the ALK fusion product, which, of course, is actionable in lung cancer and is actionable with the drug crizotinib, but we don’t now that that would be the same in colon cancer. And I think this technology is nascent technology. So it doesn’t diminish the scientific value and the incredible technology that they’re bringing to bear, but this particular paper I don’t think really helps the field very much.
DR LOVE: Alan, do you think crizotinib could work in these patients?
DR VENOOK: It may, but I think the sobering message — the excitement of BRAF mutations in melanoma is the best example, which is — of course, the waterfall plot looked like Niagara Falls.
In colon cancer, the same strategy with BRAF really had no impact in the disease. We presented some data with BRAF and MEK inhibitors where we saw transient responses in colon cancer. So I think there may be a thread through these diseases, but some diseases will undoubtedly be more dependent on these pathways than others. And so it’s great to challenge colon cancers with ALK fusion products with crizotinib, but are we likely to see responses? We don’t know until we do the experiment. But it won’t necessarily transfer from one disease to the next.
DR FUCHS: I think Alan makes a great point, which is that one size doesn’t fit all here. That is, clearly a BRAF mutation in melanoma doesn’t seem to have the same effect in colorectal cancer because the BRAF inhibitors don’t work. And what I think it suggests is you’ve got to look at context, that any one dimension, be it a gene expression or sequence data alone, is not going to tell you the answer about how to treat a patient. You really are going to need multi-dimensional data so that if you look at a BRAF mutation you know what it’s occurring in and in what context. Because that may decide whether you give a patient a BRAF inhibitor alone or, potentially, with other drugs that make that more effective.