Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Mol Oncol. 2011 Apr;5(2):116-23. doi: 10.1016/j.molonc.2011.01.005. Epub 2011 Feb 16.
Activating mutations in BRAF, a constituent of the map kinase pathway, were first discovered as being most prevalent in melanoma in 2002. Only recently have potent and selective, orally available inhibitors of BRAF emerged for clinical testing and demonstrated clear evidence of tumor regression in the majority of patients whose tumors harbor a BRAF mutation. While these early observations suggest that the BRAF targeted therapy will become part of the standard treatment paradigm for patients with advanced melanoma, it is also clear that a majority of these responses are incomplete and temporary. Therefore, the focus of the melanoma field has shifted to understanding the limits of the first generation of selective BRAF inhibitors with regard to safety and efficacy, the context of somatic genetic changes that accompany BRAF, and the combination regimens that target distinct elements of melanoma pathophysiology.
BRAF 是丝裂原活化蛋白激酶（MAPK）通路的组成部分，其激活突变于 2002 年首次被发现，在黑色素瘤中最为常见。直到最近，才出现了针对 BRAF 的高效、选择性、口服可用抑制剂，这些抑制剂已经进入临床试验，并在大多数携带 BRAF 突变的肿瘤患者中显示出明确的肿瘤消退证据。尽管这些早期观察结果表明，BRAF 靶向治疗将成为晚期黑色素瘤患者标准治疗方案的一部分，但也很明显，这些反应大多数并不完全且是暂时的。因此，黑色素瘤领域的重点已转移到了解第一代选择性 BRAF 抑制剂在安全性和有效性方面的局限性、伴随 BRAF 的体细胞遗传变化的背景，以及针对黑色素瘤病理生理学不同元素的联合治疗方案。
