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Sept. 2, 2009 -- People with advanced skin and brain cancers -- untreatable by current methods -- improve after treatment with a new oral drug called a hedgehog inhibitor.
Hedgehog is one of the hottest new anticancer targets. During embryonic development and childhood, the signaling molecule nicknamed hedgehog spurs growth processes. But the body turns it off during adulthood. When hedgehog isn't turned off, it promotes the growth of cancer cells.
An experimental drug code-named GDC-0449 by developer Genentech blocks hedgehog. Can it fight cancer?
Some cancer types are particularly dependent on hedgehog. One is basal cell carcinoma, the most common skin cancer in the U.S. Although surgery can cure this cancer in early disease, metastatic disease has no standard treatment and usually is rapidly fatal.
Can GDC-0449 help? In a Genentech-funded study, Daniel D. Von Hoff, MD, of Scottsdale Healthcare and colleagues gave the drug to 33 patients with inoperable metastatic or locally advanced basal cell carcinoma.
"The overall response rate was 55%, with a remarkable response rate of 50% in 18 patients with metastatic disease," University of Michigan researchers Andrzej A. Dlugosz, MD, and Moshe Talpaz, MD, note in an editorial accompanying the study in the Sept. 2 online edition of The New England Journal of Medicine.
Only four of the patients had continued progression of their cancers over the course of the 10-month study. There were relatively few adverse events linked to the treatment.
In another Genentech-funded study published in the same issue of The New England Journal of Medicine, Johns Hopkins researcher Charles M. Rudin, MD, PhD, and colleagues report the treatment of a brain cancer -- medulloblastoma -- with GDC-0449.
Medulloblastoma -- cancer of the part of the brain called the cerebellum -- usually strikes at about age 5 years. But it can strike in early adulthood, too. The patient seen by Rudin and colleagues was 26, and had been fighting the disease for four years. Most people die of this cancer in less than six months.
The man survived extensive surgeries, radiation therapies, and chemotherapies. But at the time he was treated with GDC-0449, scans showed that the cancer had spread painfully throughout his body.
After two months of treatment, the same scans showed astonishingly fewer tumors, and the patient's pain decreased. He even gained weight.
Unfortunately, within three months the cancer had become resistant to GDC-0449. It already had returned throughout his body; two months later, the man died.
Dlugosz and Talpaz note that as a future cancer treatment, GDC-0449 likely will be used in combination with surgery and other treatments.
Other companies are working on hedgehog inhibitors. There is evidence that this class of drug may be helpful in many different cancer types.
"The remarkable responses that are reported in initial cases suggest that the hedgehog pathway can be the basis of an important new class of therapeutic agents with far-reaching implications in oncology," Dlugosz and Talpaz conclude.