Results from a phase 1 study published in September indicate that GDC-0449, an orally active small molecule targeting the hedgehog pathway developed by S. San Francisco, California–based Genentech, has potent antitumor activity. More than half the patients with advanced and inoperable skin cancer treated with GDC-0449 responded to treatment (New Engl. J. Med. 361, 1164–1172, 2009.) “It was a very, very nice proof of concept,” says Steve Gendreau, associate director, clinical science, at Exelixis, of S. San Francisco, which is also developing a hedgehog pathway inhibitor.
A case report in the same issue of the New England Journal of Medicine (361, 1173–1178, 2009) describes how GDC-0449—a compound developed from a research collaboration initiated with Cambridge, Massachusetts–based Curis in 2003—resulted in rapid tumor regression and improvement of symptoms in a patient with a highly drug-resistant, metastatic form of brain cancer called medulloblastoma. As is often the case with targeted cancer treatments, however, the remarkable initial response was reversed when the patient developed a drug-resistant mutation.
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