Newswise — June 6, 2012, Oakland, Calif. – A revolutionary clinical study has demonstrated the effectiveness of a new drug, vismodegib, in dramatically shrinking and preventing the formation of basal cell skin cancers – the most common cancer in the United States – in patients with basal cell nevus syndrome (BCNS), a rare genetic condition that causes hundreds to thousands of skin cancers primarily treated by surgical removal.

The study, led by Children’s Hospital Oakland Research Institute (CHORI) Senior Scientist and dermatologist Ervin H. Epstein, Jr., MD, and David R. Bickers, MD, of New York-Presbyterian Hospital/Columbia University Medical Center, was published online today in the New England Journal of Medicine.

“Patients in our study showed a dramatic reduction both in the growth of existing tumors and in the development of new tumors,” said Dr. Epstein. “The trial results were even better than we had hoped, with patients showing improvement in just one month of treatment. Not only did all the basal cell cancer tumors respond to treatment, but some subjects achieved near complete clinical remission.”

Basal cell carcinomas (BCCs) are the hallmark of BCNS, also known as Gorlin syndrome, which also has defects in many other tissues. BCNS is caused by a heritable mutation first identified by Dr. Epstein and collaborators as well as others independently using National Institutes of Health (NIH) funding in 1996.

People with BCNS inherit one defective copy of a gene called PTCH1, which under normal conditions acts as a tumor suppressor by inhibiting a very common signaling pathway, called the hedgehog (HH) signaling pathway. However, in BCNS patients, the loss in the skin of the second, normal copy of PTCH1 gene causes an increase in HH signaling, and tumors grow unchecked.

Vismodegib is a small molecule that replaces the function of the missing/defective PTCH1 gene and thereby inhibits the hedgehog signaling pathway.

This study was the first to evaluate the effectiveness of this drug in patients with BCNS. The randomized double-blind study included 42 participants receiving either oral vismodegib (control group) or a placebo for a planned maximum participation of 18 months.

Patients on the drug experienced an annual average of 2.3 new surgically eligible basal cell cancers compared to an average of 29 for the patients in the placebo group. In addition to a decreased frequency of tumors, the size of the control group’s tumors present at the start of the study decreased by an average of 65 percent. The results were so dramatic that the study’s data and safety monitoring board recommended switching all participants to the drug only 15 months after the first patient was enrolled.

The results of the study are already creating a major impact. On January 30, 2012, the Food and Drug Administration (FDA) approved vismodegib, manufactured by Genentech, Inc., for use in adults with metastatic and recurrent BCCs untreatable with surgery or radiation.

The treatment produces some annoying adverse effects including muscle cramps and hair loss, so future research will focus on limiting these side effects while still maintaining the effectiveness of treatment.

While vismodegib is currently a treatment for BCNS, there is the potential for the drug to treat dozens of other cancers in which tumor growth is linked to abnormal activation of the hedgehog signaling pathway.

About Children’s Hospital & Research Center OaklandChildren’s Hospital & Research Center Oakland is Northern California’s only independent not-for-profit regional medical center for children. Children’s Hospital Oakland is a national leader in many pediatric specialties and sub-specialties including hematology/oncology, neonatology, cardiology, orthopedics, sports medicine, and neurosurgery. The hospital is one of only two solely designated California Level 1 pediatric trauma centers with the largest pediatric inpatient critical care unit in the region. Children’s Hospital has 190 licensed beds, 201 hospital-based physicians in 30 specialties, more than 2,700 employees, and an annual operating budget of more than $350 million. Children’s is also a premier teaching hospital with an outstanding pediatric residency program and a number of unique Pediatric subspecialty fellowship programs.

Children’s research program, Children’s Hospital Oakland Research Institute (CHORI), is known internationally for state-of-the-art basic and clinical research and translating it into interventions for treating and preventing human diseases. CHORI has 300 members of its investigative staff, a budget of about $50 million, and is ranked among the nation’s top 10 research centers in National Institutes of Health funding to children’s hospitals. For more information, go to and

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New England Journal of Medicine (366;23)