New Compound Shrinks Skin Cancers

Study found more than half of advanced basal cell carcinomas responded to treatment

By Amanda Gardner
HealthDay Reporter

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WEDNESDAY, Sept. 2 (HealthDay News) -- An experimental cancer drug that switches off the so-called "Hedgehog" pathway beat back tumors in more than half of patients with advanced basal cell carcinoma, a type of skin cancer.

The drug also helped a 26-year-old man suffering from medulloblastoma, the most common form of brain cancer in children.

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"We were both pleased and surprised. We had hoped that we might see responses like this but we in no way anticipated that, within the context of a phase 1 clinical trial, we would see this level of anti-tumor activity," said Dr. Charles M. Rudin, who authored two papers on the findings that appear in the Sept. 2 online edition of the New England Journal of Medicine. "These are the first reports in the literature of any Hedgehog inhibitor being used clinically."

Phase 1 trials are conducted to look at a drug's safety profile and determine the right dose. Phase 2 and phase 3 trials typically look at effectiveness.

Also exciting, however, is the fact that the Hedgehog pathway has been implicated in other cancers, notably colon cancer and ovarian cancer, albeit in a different way.

Researchers are going forward to look at the potential of the molecule, known as GDC-0449, to treat these types of cancers as a one-drug regimen, and in combination with other drugs for other solid tumor malignancies, said Rudin, who is associate director for clinical research at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore.

One expert noted that finding a compound that might control the Hedgehog pathway could have far-reaching implications.

"These are phase 1 trials so they're quite preliminary, but the drug is quite effective in at least a subset of the patients treated," said Dr. Andrzej Dlugosz, author of an accompanying editorial and a professor in the department of dermatology at the University of Michigan Medical School and Comprehensive Cancer Center in Ann Arbor. "The reason we're so excited is that there are now a large number of cancers that have also been linked to abnormalities in this pathway, including pancreatic, colon, ovarian and prostate. It's quite an impressive list. The data is pretty strong suggesting that if you shut down the pathway, it can have a pretty profound effect on those tumor cells. If it can work in these cancers, maybe it can work in other cancers, even though the signaling there is more complex."

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