Drug-resistant melanoma tumors shrink when therapy is interrupted

Source：University of California, San Fr Release Date：2013-01-10 254

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'Intermittent dosing' strategy in lab mice suggests simple way to help people with late-stage melanoma

RESEARCHERS in California and Switzerland have discovered that melanomas that develop resistance to the anti-cancer drug vemurafenib (marketed as Zelboraf), also develop addiction to the drug, an observation that may have important implications for the lives of patients with late-stage disease.

The team, based at the University of California, San Francisco (UCSF), the Novartis Institutes for Biomedical Research (NIBR) in Emeryville, California, and University Hospital Zurich, found that one mechanism by which melanoma cells become resistant to vemurafenib also renders them “addicted” to the drug. As a result, the melanoma cells nefariously use vemurafenib to spur the growth of rapidly progressing, deadly and drug-resistant tumors.

As described this week in the journal Nature*, the team built upon this basic discovery and showed that adjusting the dosing of the drug and introducing an on-again, off-again treatment schedule prolonged the life of mice with melanoma.

“Remarkably, intermittent dosing with vemurafenib prolonged the lives of mice with drug-resistant melanoma tumors,” said co-lead researcher Martin McMahon, PhD, the Efim Guzik Distinguished Professor of Cancer Biology in the UCSF Helen Diller Family Comprehensive Cancer Center.

It is therefore possible that a similar approach may extend the effectiveness of the drug for people – an idea that awaits testing in clinical trials.

Investigated through a public-private partnership, the research was spearheaded by the study’s first author Meghna Das Thakur, PhD, a Novartis Presidential Postdoctoral Fellow, who was co-mentored by McMahon at UCSF and Darrin Stuart, PhD at NIBR.

McMahon is supported by the Melanoma Research Alliance, the National Cancer Institute and the UCSF Helen Diller Family Comprehensive Cancer Center, which is one of the country’s leading research and clinical care centers, and is the only comprehensive cancer center in the San Francisco Bay Area.

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