Breaking BRAF(V600E)-drug resistance by stressing mitochondria

Abstract

Until recently, advanced stage melanoma was considered an untreatable disease. However, tangible hope for patients has now become attached to small molecule inhibitors targeting the melanoma oncogene BRAF(V600E) and approaches to unleash the immune system against these tumors. Still, not every patient will be given respite by these treatments, and the ultimate goal of durable disease remission remains elusive. While the barriers to achieving durable responses remain incompletely understood, eventual relapse is likely a consequence of a variable degree of cancer heterogeneity that enables selective outgrowth of treatment resistant tumor clones. However, identification of alternative molecular targets that could be harnessed for combinatorial use hold promise to extend these initial responses, and may afford sustainable treatment.

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