Combination of RAF and MEK Inhibition for the Treatment of BRAF-Mutated Melanoma: Feedback Is Not Encouraged

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Abstract

In BRAF V600E melanoma patients, RAF inhibitor treatment causes a MEK-inhibitor-sensitive, RAF-inhibitor-resistant adaptive reactivation of ERK signaling. In clinical trials combining MEK and RAF inhibitors, therapeutic efficacy was modestly enhanced, suggesting the utility of inhibiting feedback-reactivated pathways. Strategies for optimally inhibiting ERK signaling should be explored. In BRAF V600E melanoma patients, RAF inhibitor treatment causes a MEK-inhibitor-sensitive, RAF-inhibitor-resistant adaptive reactivation of ERK signaling. In clinical trials combining MEK and RAF inhibitors, therapeutic efficacy was modestly enhanced, suggesting the utility of inhibiting feedback-reactivated pathways. Strategies for optimally inhibiting ERK signaling should be explored.

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Chapman, P. B., Solit, D. B., & Rosen, N. (2014, November 10). Combination of RAF and MEK Inhibition for the Treatment of BRAF-Mutated Melanoma: Feedback Is Not Encouraged. Cancer Cell. Cell Press. https://doi.org/10.1016/j.ccell.2014.10.017

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