Vemurafenib and BRAF Inhibition: A New Class of Treatment for Metastatic Melanoma
Vemurafenib and BRAF Inhibition: A New Class of Treatment for Metastatic Melanoma
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DOI：
10.1158/1078-0432.ccr-11-2197
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发表时间：
2012-01-01
影响因子：
11.5
通讯作者：
Hodi, F. Stephen
中科院分区：
文献类型：
--
作者：
Luke, Jason J.;Hodi, F. Stephen
美国食品和药物管理局最近批准vemurafenib用于治疗BRAF外显子15中密码子600处的缬氨酸（V600 E）突变转移性黑色素瘤。维罗非尼是一种竞争性小分子丝氨酸-苏氨酸激酶抑制剂，通过与突变型BRAF的ATP结合结构域结合发挥作用。与达卡巴嗪化疗相比，vemurafenib显著改善了患者的6个月总生存率，从64%提高到84%，缓解率约为50%。与达卡巴嗪相比，vemurafenib组的中位无进展生存期也显著改善（分别为5.3个月和1.6个月），这在分析的各组中一致，包括年龄，性别，地理位置，东部肿瘤协作组状态，疾病分期和血清乳酸脱氢酶。靶向黑色素瘤基因组学的成功为未来的药物开发创造了一个范式转变。目前，对维罗非尼治疗的耐药机制的阐明仍然是积极研究的重要领域，这将塑造黑色素瘤的合理药物治疗。vemurafenib的发展，BRAF靶向的作用以及黑色素瘤治疗的变化为临床研究提供了新的基础。临床癌症研究; 18（1）; 9-14。(C)2011年AACR。
The U.S. Food and Drug Administration recently approved vemurafenib for the treatment of BRAF valine in exon 15, at codon 600 (V600E) mutant metastatic melanoma. Vemurafenib is a competitive small-molecule serine-threonine kinase inhibitor that functions by binding to the ATP-binding domain of mutant BRAF. Compared with dacarbazine chemotherapy, vemurafenib significantly improved the 6-month overall survival of patients from 64% to 84% and exhibited a response rate of approximately 50%. Median progression-free survival was also significantly improved with vemurafenib as compared with dacarbazine (5.3 versus 1.6 months, respectively), and this was consistent among groups analyzed, including age, sex, geography, Eastern Cooperative Oncology Group status, disease stage, and serum lactate dehydrogenase. The success of targeting melanoma genomics has created a paradigm shift for future drug development. Currently, the elucidation of resistant mechanisms to vemurafenib therapy remains an important area of active investigation that will shape rational drug treatments for melanoma. The development of vemurafenib, the role of BRAF targeting, and the changing landscape of treatment for melanoma provide a new foundation for clinical investigation. Clin Cancer Res; 18(1); 9-14. (C) 2011 AACR.