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New screening approach identified potential drug combos for difficult-to-treat melanomas
Date:12/13/2012

PHILADELPHIA A novel approach to identifying potential anticancer drug combinations revealed that pairing cholesterol-reducing drugs called statins with cyclin-dependent kinase inhibitors might provide an effective approach to treating intractable melanomas driven by mutations in the NRAS and KRAS gene.

David F. Stern, Ph.D., professor of pathology at Yale University School of Medicine in New Haven, Conn., and colleagues reported these data in Cancer Discovery, a journal of the American Association for Cancer Research.

"The identification of gene mutations that drive specific subsets of cancers has had a major beneficial impact on treatments for these patients. But, such mutations can only be identified for some cancers. Some patients who have a specific cancer-driving genetic mutation never respond to the matching drug, while nearly all those who initially respond eventually become resistant to the effects of the drug and their cancers relapse," said Stern.

For this reason, Stern and colleagues reasoned that using drug combinations may be necessary to address the problem of drug resistance and enable effective treatment of cancers driven by signaling molecules that currently cannot be targeted, such as RAS.

They developed an in vitro, high-throughput screen to test the effectiveness of anticancer drugs, alone and in pairs, against three types of melanoma cell lines: those driven by mutations in the RAS gene (representing approximately 20 percent of human melanomas), those driven by mutations in the BRAF gene (40 to 50 percent of melanomas) and those without mutations in either the RAS or BRAF genes.

Through analysis of 150 drugs as single agents, Stern and colleagues narrowed their pool to 40 drugs for combination testing. Melanoma cell lines driven by BRAF and RAS were sensitive to different combinations of drugs. Some combinations that killed BRAF-driven melanoma cell lines were also effective agains
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Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

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