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Assays & screens

High throughput combinatorial screening to identify genotype-selective combination therapies for melanoma

High throughput combinatorial screening could be useful for identifying genotype-selective combination therapies to treat melanoma. The combinatorial screen tested a curated panel of 150 small molecule chemotherapy or targeted therapies against melanomas with activating mutations in BRAF or Ras or those with wild-type forms of the genes. Inhibition of both epidermal growth factor receptor (EGFR) and protein kinase B (PKB; PKBA; AKT; AKT1) sensitized treatment-resistant BRAF mutant melanomas to Zelboraf vemurafenib. The screen also found that Ras-mutant melanomas were sensitive to the combination of statins and cyclin dependent kinase (CDK) inhibitors. Next steps include running additional animal studies.
Roche, Chugai Pharmaceutical Co. Ltd. and Daiichi Sankyo Co. Ltd. market the BRAF inhibitor Zelboraf to treat melanoma.

SciBX 6(2); doi:10.1038/scibx.2013.41
Published online Jan. 17, 2013

Unpatented; licensing status not applicable

Held, M.A. et al. Cancer Discov.; published online Dec. 13, 2012;
Contact: David F. Stern, Yale School of Medicine, New Haven, Conn.