Hagen Brenda, Trinh Van Anh
University of Texas MD Anderson Cancer Center, Houston, Texas.
J Adv Pract Oncol. 2014 Nov-Dec;5(6):400-10.
Somatic point mutations in the BRAF gene have been found in approximately 50% of melanomas. BRAF (V600E), the most common mutation, results in the constitutive activation of BRAF (V600E) kinase, sustaining MAPK signaling and perpetuating cell growth. This groundbreaking discovery led to the clinical development of vemurafenib, a selective BRAF inhibitor. Vemurafenib has been approved for the treatment of patients with BRAF (V600E)-positive unresectable or metastatic melanoma based on survival benefit demonstrated in a randomized phase III study. The current approved dosing schedule of vemurafenib is 960 mg orally twice a day until disease progression or unacceptable toxicity. Vemurafenib is well tolerated, with the most common adverse effects including skin reactions, photosensitivity, headache, and arthralgia. Active research is ongoing to expand the utility of vemurafenib into the adjuvant setting and to circumvent rapid emergence of drug resistance.
在大约50%的黑色素瘤中发现了BRAF基因的体细胞点突变。BRAF（V600E）是最常见的突变，导致BRAF（V600E）激酶的组成性激活，维持MAPK信号传导并使细胞生长持续。这一开创性的发现促成了选择性BRAF抑制剂维莫非尼的临床开发。基于一项随机III期研究中显示的生存获益，维莫非尼已被批准用于治疗BRAF（V600E）阳性不可切除或转移性黑色素瘤患者。目前批准的维莫非尼给药方案是口服960mg，每日两次，直至疾病进展或出现不可接受的毒性。维莫非尼耐受性良好，最常见的不良反应包括皮肤反应、光敏反应、头痛和关节痛。目前正在进行积极的研究，以扩大维莫非尼在辅助治疗中的应用，并规避耐药性的快速出现。
