Targeting mutant BRAF in melanoma: current status and future development of combination therapy strategies.
Targeting mutant BRAF in melanoma: current status and future development of combination therapy strategies.
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DOI：
10.1097/ppo.0b013e31824b436e
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Smalley KS
中科院分区：
文献类型：
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作者：
Kudchadkar R;Paraiso KH;Smalley KS
The discovery of activating BRAF mutations in ~50% of all melanomas has proved to be a turning point in the therapeutic management of the disseminated disease. In this commentary we review the latest research delineating the role of mutant BRAF in melanoma initiation and progression and discuss the remarkable 10-year journey leading up to the recent FDA-approval of the small molecule BRAF inhibitor vemurafenib. We further outline the most recent findings on the mechanisms that underlie intrinsic and acquired BRAF inhibitor resistance and describe ongoing preclinical and clinical studies designed to delay or abrogate the onset of therapeutic escape. It is hoped that our evolving understanding of melanoma genetics and intracellular signaling coupled with a growing armamentarium of signal transduction inhibitors will lead to significant improvements in the level and durability of therapeutic response in metastatic melanoma.
