Drug-Resistant Melanoma Finding May Improve Treatment Approach

Scientists have discovered how cancer develops resistance against a new melanoma treatment from Roche Holding AG (ROG), a finding that could help extend lives of some patients.

Roche’s Zelboraf, a so-called BRAF inhibitor, works by blocking a protein that fuels tumor growth in about half of patients with advanced forms of the skin cancer. Zelboraf, cleared for sale in the U.S. in August, eventually stops working as the cancer spurs production of a different version of the protein that the drug is designed to block, researchers found.

While the Roche medicine worked better at prolonging survival and shrinking tumors than chemotherapy, patients develop a resistance to the therapy within a year, said David Solit, an author of the study. Knowing how the cancer fights back could help fuel new therapies and, in particular, a combination approach to extend life, much like HIV/AIDS medicines, Solit said.

“They have this dramatic response to the treatment, but then after six or nine months, the tumor progresses on the drug,” Solit, an associate member and attending physician at Memorial Sloan-Kettering Cancer Center in New York, said in an interview. “People have been pretty interested in figuring out why the resistance develops, so that’s what we’ve been looking into.”

Zelboraf was developed by Roche, of Basel, Switzerland, and Plexxikon Inc., which was acquired by Tokyo-based Daiichi Sankyo Co. Other companies working on BRAF inhibitors include Amgen Inc. (AMGN), GlaxoSmithKline Plc (GSK), Novartis AG (NOVN) and Pfizer Inc. (PFE), according to the Bloomberg drug database.

New Drugs

“It’s possible that you could develop either a combination of drugs or simply a single drug, a different RAF inhibitor, that would be resistant to this mechanism and therefore could have a longer duration of activity,” Solit said.

More than 68,000 Americans were diagnosed with melanoma last year, according to the National Cancer Institute. The five- year survival rate is 15 percent among patients diagnosed after the cancer has spread. When caught in its early stages, the disease has a 98 percent survival rate after five years.

The study was published in the journal Nature.

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net.

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