Yale School of Medicine, New Haven, Connecticut, USA.
Clin Cancer Res. 2012 Jan 1;18(1):33-9. doi: 10.1158/1078-0432.CCR-11-0997.
The efficacy of selective BRAF inhibitors has now been established in the 50% of patients with metastatic melanoma whose tumors harbor activating mutations. However, for the vast majority of patients, responses persist for less than a year. In extensive preclinical investigations, researchers have focused on potential resistance mechanisms with the hope of identifying treatment strategies that can overcome resistance. Preliminary results suggest that reactivation of the mitogen-activated protein kinase (MAPK) pathway by several BRAF-independent mechanisms is the predominant pattern. However, MAPK pathway-independent mechanisms also seem to play a potential role. More definitive cataloging of resistance mechanisms in patients' tumor samples is needed as combination regimens are being readied for clinical evaluation.
选择性 BRAF 抑制剂的疗效现已在 50%携带激活突变的转移性黑色素瘤患者中得到证实。然而，对于绝大多数患者来说，反应持续时间不到一年。在广泛的临床前研究中，研究人员专注于潜在的耐药机制，希望找到可以克服耐药性的治疗策略。初步结果表明，几种 BRAF 非依赖性机制重新激活丝裂原活化蛋白激酶（MAPK）途径是主要模式。然而，MAPK 途径非依赖性机制似乎也起着潜在作用。随着联合治疗方案准备进行临床评估，需要对患者肿瘤样本中的耐药机制进行更明确的分类。
