June 04, 2012 Edward A. Sausville, M.D., Ph.D., discusses the promise of a new targeted drug therapy for advanced melanoma in an editorial in the New England Journal of Medicine published online on June 4, 2012. A medical oncologist and pharmacologist, Dr. Sausville is a professor of medicine at the University of Maryland School of Medicine and associate director for clinical research at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.
In the editorial, Dr. Sausville comments on a study that found that a single daily dose of the drug trametinib decreased tumor progression by about three months in patients with melanoma whose tumor cells had a particular mutation in a gene known as BRAF, compared with patients who received chemotherapy. Patients also experienced improved overall survival, with a 14 percent greater chance of being alive after six months.
Melanoma is the most dangerous form of skin cancer and is responsible for more than 8,700 deaths in the U.S. each year. Two-thirds of melanomas are associated with a mutation in the BRAF gene, which activates a number of proteins involved in cell growth and survival through a complex signaling pathway within the cell. The drug trametinib targets a specific protein that plays a key role in the activation of this pathway. Trametinib is what is called a MEK inhibitor.
“The challenge for researchers is to understand how signaling pathways within cells affect the ability of tumor cells to survive and grow unchecked,” says Dr. Sausville. He notes that only 22 percent of the patients had a complete or partial response to the therapy, compared to less than 10 percent for chemotherapy. Although the signaling pathway may be important, “how that pathway connects to the maintenance of tumor-cell viability (and potential for clinical shrinkage) is unclear and should be the focus of further investigation,” he notes in the editorial.
Dr. Sausville says that although trametinib looks promising, researchers are also studying whether other MEK inhibitors will affect tumors with other gene mutations.
He also suggested that it would be worthwhile to conduct pre-clinical testing of trametinib in combination with other drugs to define their value in tumors without a BRAF gene mutation that are activated through other pathways.
Dr. Sausville’s research at the University of Maryland Greenebaum Cancer Center focuses on early-stage clinical trials of new drugs for cancer treatment. He came to the University of Maryland in 2004 from the National Cancer Institute (NCI), where he was associate director of the Division of Cancer Treatment and Diagnosis for the Developmental Therapeutics Program. The program directs NCI’s preclinical anti-cancer drug development portfolio.