Hedgehog drugs begin to show results.

W hen re searchers an nounced last month that a hedgehog pathway inhibitor from Ge nentech had shown activity in a phase I cancer clinical trial, few noticed. Phase I results are usually suggestive at best. But in this trial, eight of nine patients with advanced basal cell carcinoma responded to the Ge nentech drug, and all eight are still enrolled 16 months into the study. “The first patient in the world gets treated with an inhibitor of this pathway and has a dramatic response,” noted principal investigator Daniel Von Hoff , M.D., of the Translational Genomics Research Institute in Phoenix, Ariz., at the annual meeting of the American Association for Cancer Research. “That ... is the essence of translational medicine.” It was also probably the fi rst time that a cancer drug specifi cally targeting a developmental pathway has shown activity in people. The hedgehog pathway is critical for embryonic and postnatal organ and tissue development, and the Genentech results validated, at least for now, the emerging concept of cancer as a disease of normal development gone awry. At least fi ve drug companies are working on antitumor hedgehog pathway blockers, and the coming years will probably see more drug candidates make their debut in the clinic against many forms of cancer.