In This Section      
Print This Page

Promise and Progress - New Anticancer Drug for Skin and Brain Cancers

Leading the Way Fall 2009 Winter 2010

New Anticancer Drug for Skin and Brain Cancers

By: Valerie Mehl
Date: December 1, 2009

New England Journal of Medicine and Science Express, September 3, 2009

As more is understood about the genetic mutations of specific cancers, new therapies that target these factors responsible for malignant growth are being developed and tested.
The Hedgehog signaling pathway, normally active only in embryonic development, gets reactivated in some cancer types. An experimental drug that blocks this pathway has shown impressive activity in patients with advanced basal cell skin cancer and
with a cancer called medulloblastoma. Basal cell skin cancer is the most common malignancy in adults, and medulloblastoma is the most common brain cancer in children.

In the study, 33 basal cell skin cancer patients were given the new drug. Eighteen patients had advanced disease that had spread to other organs, and half of them saw reductions in
tumor size by 50 percent or more. Nine of 15 patients with inoperable recurrences at the original tumor site also had favorable responses, including two with complete disappearance of the tumors.

“We know that basal cell skin cancers and medulloblastomas have mutations in Hedgehog pathway genes. The favorable responses we are seeing with Hedgehog inhibitors could lead to new therapies for these intractable cancers,” says Charles Rudin, M.D., Ph.D., who helped direct the multi-center study.

Rudin and team gave the drug to a 26-year-old patient, with advanced medulloblastoma, whose cancer had recurred after standard therapy and did not respond to other treatments.

“Within a few weeks of treatment, this patient went from being nearly bedridden and in significant pain to exercising and pain-free.” Rudin says. Sadly, two months later, the drug stopped working, and the patient died later that year. Rudin and team have since  uncovered what caused the patient’s cancer to become resistant to the new drug in the form of another gene mutation that prevents the drug from hitting its target. The
team is working on ways to manage the acquired drug resistance that will allow patients to maintain the initial good response.

Clinical trials of the experimental drug in children with medulloblastoma and in adults with advanced basal cell skin cancer have begun in cancer centers throughout the U.S.
Genentech funded the research.