Division of Dermatology, Department of Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, 52-121 CHS, 10833 Le Conte Ave, Los Angeles, CA 90095-1750, USA.
Cell Res. 2012 Jun;22(6):945-7. doi: 10.1038/cr.2012.78. Epub 2012 May 8.
The BRAF inhibitors (BRAFi) induce anti-tumor responses in nearly 60% of patients with advanced -mutant melanomas but only 5% of patients with -mutant colorectal carcinomas. Earlier studies of how a subset of melanoma that initially responds to BRAFi but later acquires drug resistance pointed to the importance of receptor tyrosine kinases (RTKs) in drug escape. In a pair of recent reports, this RTK-mediated mechanism of acquired BRAFi resistance in melanoma is re-surfacing in the context of innate or primary BRAFi resistance in -mutant colorectal carcinomas, suggesting potential upfront therapeutic strategies to prevent BRAFi resistance.
BRAF 抑制剂（BRAFi）在近 60%的晚期 -突变黑色素瘤患者中引发抗肿瘤反应，但在 -突变结直肠癌患者中只有 5%。先前的研究表明，最初对 BRAFi 有反应但后来产生耐药性的一部分黑色素瘤如何逃避药物，这表明受体酪氨酸激酶（RTKs）在药物逃逸中的重要性。在最近的两份报告中，这种 RTK 介导的黑色素瘤获得性 BRAFi 耐药机制在 -突变结直肠癌的先天或原发性 BRAFi 耐药中重新出现，提示潜在的预防性治疗策略以防止 BRAFi 耐药。
