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GDC-0449 shows potential in treating pancreatic cancer
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In honor of pancreatic cancer awareness month, I thought I would bring you my impression of a potentially important mechanism in pancreatic adenocarcinoma. It has been known that the stroma may play a particularly important role in the development and progression of pancreatic carcinoma. There are now some drugs that can target the hedgehog pathway, and in doing so, can also potentially target the stroma in pancreatic cancer. The most developed of these appears to be GDC-0449, an oral smoothened inhibitor.
You may have seen two recent articles in The New England Journal of Medicine that centered on GDC-0449. One was the phase-1 study in basal cell cancers, which had an impressive nearly 55% response rate and a median duration of 9.8 months. Adverse events didn't sound terrible — fatigue, hyponatremia, muscle spasm, one case of atrial fibrillation. The other was a case report (a case report! In the NEJM!) of a patient with medulloblastoma who had an impressive but transient response to GDC-0449 after a large amount of disease and prior therapy.
Neither of these disease responses were surprises — both are thought to be very dependent on the sonic hedgehog pathway. But they do provide a proof of principle and give us valuable information on this novel drug target as we work to bring it to other, more common malignancies. I see on clinicaltrials.gov that there are ongoing clinical trials investigating GDC-0449 and gemcitabine as well as GDC-0449 and erlotinib (Tarceva, OSI Pharmaceuticals), which are currently enrolling patients, and I look forward to those results.
Forward progress in pancreatic adenocarcinoma would likely be the "big event" of my career — and I hope it happens soon.