RTP On Demand — Head & Neck/Thyroid | Research To PracticeCharacteristics of thyroid cancer influencing treatment
3:23 minutes.
TRANSCRIPTION:
DR COHEN: Thyroid cancer ironically is a disease where we knew a lot about the molecular biology before we had agents to actually treat it. And we knew that this was an angiogenic disease. We knew that it was very vascular. We knew that there were BRAF mutations, RAS mutations, some rearrangements. Those had all been described. We just didn’t have the agents to treat the disease. And so, fortunately, now we do. The agents, of course, that are at the forefront of therapy are the VEGF TKIs. And that has to do really with the biology of the disease. It’s not necessarily a mutation or a genetic alteration, but these are vascular tumors that express the receptors, that express the ligands and, to some degree, depend on the vasculature for their propagation and sustenance. We’ve known for a long time that VEGF is highly expressed and can be prognostic in this disease. We know that the receptor systems, all three, VEGF1, 2 and 3, are expressed in thyroid cancers. And so we have had a sense that anti-angiogenics may be, in fact, quite active in this disease. DR LOVE: What about agents such as bevacizumab or VEGF trap, aflibercept? DR COHEN: It’s interesting. So, despite what I just said, when we applied those agents, so ligand-targeting agents, to differentiated thyroid cancers, we saw no activity. And I don’t have a good explanation for that. We hypothesize that maybe the small molecules are targeting something in the kinase domain, a mutation or an alteration on the kinase domain, that makes them effective, whereas inhibiting a ligand doesn’t. But we weren’t able to demonstrate that. So I don’t know why that is. We do know that there are genetic alterations in thyroid cancer, with the most common one being BRAF. BRAF is mutated in about 50% of papillary thyroid cancers. And clearly it’s an activating mutation. It’s the same mutation that we see in melanoma and more rarely in lung cancer and some other solid tumors. Beyond BRAF, we know that RAS is often mutated, especially in follicular thyroid cancer. So KRAS, NRAS and even sometimes HRAS, but KRAS and NRAS are the most common. And then we do know that there are even mutations in other kinases, such as MET, that haven’t been exploited as much as the others, but they do exist, and mutations in the PI3 kinase pathway, especially in that critical gene, PIK3CA, again, something that hasn’t been exploited therapeutically, but things that we’re interested in studying. DR LOVE: How about EGFR? DR COHEN: EGFR is interesting. EGFR is, as with many other solid tumors, it’s expressed in thyroid cancers and expressed quite robustly in these tumors. But trials with single-agent EGFR inhibitors really have not shown very promising activity. And it’s a case of the target’s there, but it’s not genetically altered. And inhibiting the target doesn’t seem to do anything to the tumor. |