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Moving Forward: Making BRAF-Targeted Therapy Better

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BRAF Targets in Melanoma

Part of the book series: Cancer Drug Discovery and Development ((CDD&D,volume 82))

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Abstract

For half of the advanced melanoma population, selective BRAF inhibitor therapy has transformed the natural history of disease and provided a platform for developing molecularly targeted therapy combinations. The clinical utility of vemurafenib, FDA approved BRAF inhibitor, has been validated by another potent and selective agent, dabrafenib. However, two clinical limitations of BRAF inhibitor therapy frame the problem for the melanoma field: de novo and acquired resistance. Insights into the mechanisms underlying both of these phenomena have set the stage for clinical investigation of several novel BRAF inhibitor based combination therapies. Foremost among them is the combination of a MEK inhibitor with BRAF inhibitor. Preliminary clinical evidence suggests that this combination may supplant single agent BRAF inhibitor therapy in the near future as the standard approach for metastatic patients. Yet resistance remains a challenge and strategies to target non-MAP kinase pathway dependent mechanisms are needed. This chapter will outline the preclinical evidence that supports the categorization of resistance mechanisms and the framework for clinical investigation of novel combination therapies.

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Authors and Affiliations

  1. Massachusetts General Hospital Cancer Center, 55 Fruit Street, Yawkey 9E, 02114, Boston, MA, USA

    Keith T. Flaherty MD

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  1. Keith T. Flaherty MD
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Correspondence to Keith T. Flaherty MD .

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  1. Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA

    Ryan J. Sullivan

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Flaherty, K. (2015). Moving Forward: Making BRAF-Targeted Therapy Better. In: Sullivan, R. (eds) BRAF Targets in Melanoma. Cancer Drug Discovery and Development, vol 82. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2143-0_9

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  • DOI: https://doi.org/10.1007/978-1-4939-2143-0_9

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