August 26, 2010

Grant supports melanoma research efforts

Jeffrey A. Sosman Jeffrey Sosman (Vanderbilt)

Grant supports melanoma research efforts

The Melanoma Research Alliance has awarded a three-year, $2 million grant to a multi-center team of cancer researchers investigating resistance to a new family of BRAF-targeted kinase inhibitor drugs.

These targeted therapies are being tested in melanoma patients whose tumors carry a specific genetic mutation known as V600E BRAF.

Jeff Sosman, M.D.

Jeff Sosman, M.D.

Jeff Sosman, M.D., professor of Medicine and leader of the Melanoma Program at Vanderbilt-Ingram Cancer Center, is one of the study's principal investigators.

Melanoma, a form of skin cancer, is especially lethal when it metastasizes to other areas of the body. Less than 10 percent of patients with metastatic melanoma are still alive five years after diagnosis, according to the National Cancer Institute.

About half of melanomas have a mutation in the BRAF gene. A new drug, known by its preclinical name, PLX4032, is a potent inhibitor of the most common mutant form of BRAF (V600E). In a Phase 1 clinical trial, most of the patients whose tumors expressed the BRAF mutation experienced significant tumor shrinkage, but the degree of tumor shrinkage varied greatly and many of the patients who responded eventually developed resistance to the drug.

“We need to identify the mechanisms of resistance to PLX4032 and prove that these mechanisms are clinically relevant,” said Sosman. “Our experience with targeted therapies for other forms of cancer suggests that understanding the causes of resistance will help us select the patients most likely to respond to this drug and to develop effective new drug combinations.”

Testing for specific genetic mutations and matching patients to targeted therapies for those mutations is one of the hallmarks of Vanderbilt's new Personalized Cancer Medicine Initiative. Melanoma is one of the first forms of cancer being tested at Vanderbilt for relevant genetic mutations.

All of the cancer centers involved in the study have agreed to develop a database to track the acquisition and analysis of clinical specimens, standardize the molecular testing procedures and analyze the biopsies of patients who were treated with PLX4032.

“By forming this consortium, standardizing our procedures and sharing information about tissue specimens, we hope to improve the efficiency of our research,” said Sosman. “This should allow us to speed up the development of promising therapies for this aggressive disease.”

The other Principal Investigators are: David Solit, M.D., and Paul Chapman, M.D., Memorial Sloan-Kettering Cancer Center; Michael Davies, M.D., Ph.D., MD Anderson Cancer Center; Roger Lo, M.D., Ph.D., UCLA; David Fisher, M.D., Ph.D., Keith Flaherty, M.D., and Hensin Tsao, M.D., Ph.D., Massachusetts General Hospital; and Katherine Nathanson, M.D., University of Pennsylvania.