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Diabetes drug points the way to overcoming drug resistance in melanoma
Date:6/11/2013

Advanced metastatic melanoma is a disease that has proven difficult to eradicate. Despite the success of melanoma-targeting drugs, tumors inevitably become drug resistant and return, more aggressive than before. In the current issue of the journal Cancer Cell, however, researchers at The Wistar Institute describe how they increase the effectiveness of anti-melanoma drugs by combining anticancer therapies with diabetes drugs.

Their studies, conducted in cell and animal models of melanoma, demonstrate that the combined therapy could destroy a subset of drug-resistant cells within a tumor.

"We have found that the individual cells within melanoma tumors are not all identical, and tumors contain a sub-population of cells that are inherently drug resistant, which accounts for the fact that advanced melanoma tumors return no matter how much the tumor is depleted," said Meenhard Herlyn, D.V.M., D.Sc., professor and director of Wistar's Melanoma Research Center. "We found that these slow-growing, drug-resistant cells are marked by a high rate of metabolism, which makes them susceptible to diabetes therapeutics."

"Our findings suggest a simple strategy to kill metastatic melanomaregardless of cell type within the tumorby combining anticancer drugs with diabetes drug," Herlyn said. "The diabetes drug puts the brakes on the cells that would otherwise repopulate the tumor, thus allowing the anticancer drug to be more effective."

In the Cancer Cell article, the researchers describe how various anticancer drugs, including cisplatin and the targeted therapy vemurafenib, which targets melanomas with the BRAF mutation, become more effective when co-delivered with phenformin. According to Herlyn, the researchers used the diabetes drug phenformin in their studies, but they are now working with colleagues to develop a clinical trial using a drug with less toxic side effects.

Melanoma is the deadliest, most aggressive for
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Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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