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DR MORBI: What the practicing oncologist hears a lot about in diseases other than kidney cancer is the phenomenon of driver mutations. And the driver mutation that’s druggable — for example, EGFR, ALK translocations, BCR-ABL — we have drugs that have profound effects. There is a driver mutation in kidney cancer. That driver mutation is VHL. The problem is, we do not have any drugs for the driver mutation in kidney cancer. We have drugs for the downstream effects of what the driver mutation did.

And then, when you add to that the recent data that we’ve all seen published in The New England Journal that if you biopsy kidney cancer in multiple different sites you see things that appear to be different diseases, some of them having a branch or a tree trunk, which is the VHL abnormality, but other parts of the downstream effects being very different genetically, it really speaks to a different biology for kidney cancer than what we often deal with with other solid tumors.

DR SMITH: I think this is very different than other cancers. And it’s important to recognize that at least from the clear cell cancers, that this is a disease — it’s driven by VHL inactivation. It’s the VHL biology. It’s not a VEGF biology. And VEGF is one of many factors downstream from VHL that happens to be important and that we happen to target therapeutically. That’s very different than other cancers where the angiogenesis is a phenomenon of the direct biologic abnormality in the cancer.

One of the effects of inactivation of VHL is upregulation of VEGF as a result, therefore, of angiogenesis. So this is a tumor that’s highly angiogenic from the very get go.