Beyond BRAF: where next for melanoma therapy?

Beyond BRAF: where next for melanoma therapy?
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DOI:
10.1038/bjc.2014.476
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发表时间:
2015-01-20
影响因子:
8.8
通讯作者:
Smalley, K. S. M.
Smalley, K. S. M.
中科院分区:
医学1区
文献类型:
--
作者:
Fedorenko, I. V.;Gibney, G. T.;Sondak, V. K.;Smalley, K. S. M.

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近年来,黑色素瘤已成为癌基因导向的靶向治疗发展的典型代表。这种方法以小分子BRAF抑制剂以及用于BRAF突变型黑色素瘤的BRAF/MEK抑制剂联合疗法的开发为例,给患者带来了新的希望。尽管取得了这些成功,但在大多数病例中,治疗失败似乎几乎不可避免——即使是在接受BRAF/MEK抑制剂双联疗法治疗的患者中也是如此。在本篇综述中,我们讨论了BRAF突变型黑色素瘤患者联合治疗策略的未来,以及NRAS突变型和BRAF/NRAS野生型黑色素瘤患者新出现的治疗选择。我们还概述了治疗深度个性化方面的一些最新进展,这些进展应能使黑色素瘤治疗继续塑造精准癌症医学领域。
In recent years, melanoma has become a poster-child for the development of oncogene-directed targeted therapies. This approach, which has been exemplified by the development of small-molecule BRAF inhibitors and the BRAF/MEK inhibitor combination for BRAF-mutant melanoma, has brought new hope to patients. Despite these successes, treatment failure seems near inevitable in the majority of cases—even in individuals treated with the BRAF/MEK inhibitor doublet. In the current review, we discuss the future of combination strategies for patients with BRAF-mutant melanoma as well as the emerging therapeutic options for patients with NRAS-mutant and BRAF/NRAS-wild-type melanoma. We also outline some of the newest developments in the in-depth personalisation of therapy that should allow melanoma treatment to continue shaping the field precision cancer medicine.
MEK抑制剂selumetinib(AZD6244,Arry-142886)的II期试验对BRAFV600E/K-突变的黑色素瘤患者。
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