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Hope on the Horizon
CHORI Scientists Honored for Involvement in Pioneering Skin Cancer Research

An international group of researchers dedicated to furthering the fundamental knowledge of skin and its associated diseases, the European Society for Dermatologic Research (ESDR) has been partnering with the Society for Investigative Dermatology in a world-wide investigative effort. Over the years, they have inducted as honorary members distinguished individuals whose seminal work has significantly advanced dermatological research. CHORI is pleased to announce that CHORI scientist Ervin Epstein, MD, has joined a select group of only 4 other Americans who have been so honored.

"I was lucky enough early in my career to be part of a group of researchers who had the opportunity to apply approaches devised in the more general field of human genetics to studying heritable human skin diseases."


That pioneering application of genetics to skin disease resulted in the identification of the gene responsible for a rare disorder called Basal Cell Nevus Syndrome (BCNS) in which people have many different abnormalities, including a predisposition for basal cell carcinomas, a common form of skin cancer.

"These patients may get hundreds to thousands of tumors, instead of just one or two," says Dr. Epstein. "The molecular abnormality in these rare patients with the hereditary predisposition is directly related to that in the far more common sporadic form in which these tumors just arise randomly on otherwise healthy individuals."

While these tumors rarely shorten life, they are as common as all other types of cancers put together and can result in painful surgeries, permanent scarring, and an increased public health burden. The identification of the gene responsible for BCNS, however, has opened up huge new possibilities for the treatment of all basal cell carcinomas, as well as the potential for treating other types of cancer as well.
"The key is that the genetic mutation we discovered inhibits a well-known pathway, called the hedgehog signaling pathway, which is implicated in a variety of different cancers."
"The mutation we found is responsible for the dysregulation of this pathway that drives these cancers," says Dr. Epstein.

Since the identification of this mutation, research in the area of basal cell carcinomas has grown exponentially, and the gene first implicated by Dr. Epstein's group has become an ideal target for the development of pharmaceutical inhibitors, the first of which has been developed by Genentech, and is currently being tested in several clinical trials, including a Phase II clinical study of its efficacy in BCNS patients led by Dr. Epstein himself.

"We are in the extraordinarily privileged position of not only having identified a mutation for this signaling pathway, but also leading a clinical trial for a drug that specifically replaces the function of that mutant gene in the population in which that mutation was discovered," says Dr. Epstein.
"This is an example of molecular targeted therapy at it's finest. To participate in both is an honor and a blessing. It's an excitement and reward that comes to a very few investigators."

Previous phase I trials have shown incredibly positive treatment results. Dr. Epstein's current trial is an 18-month study in collaboration with Columbia in which patients with BCNS are randomly assigned to either receive placebo or the new drug in order to determine how well it reduces the number of tumors requiring surgical intervention in this special group of high-risk patients.

"We'd like to significantly reduce the scarring, misery and cost associated with these surgeries, both in patients with this syndrome, but also in patients with the sporadic form," says Dr. Epstein.

In addition, there is some hope that targeting this mutation could also lead to treatment options for more deadly cancers as well.

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Tuesday, May 17, 2011 8:19 AM

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