文章：

KRAS-G12C抑制剂：活性和耐药性

The KRAS-G12C inhibitor: activity and resistance

原文发布日期：2021-09-01 

英文摘要：

Although it has long been deemed “undruggable”, with the development of drugs specifically binding the KRAS-G12C mutant protein, clinical trials that directly inhibit oncogenic RAS have recently made promising improvements. In particular, the covalent KRAS-G12C inhibitors sotorasib and adagrasib are used to treat patients with advanced non-small cell lung cancer (NSCLC) carrying KRAS-G12C mutations. Unfortunately, the vast majority of patients do not respond to KRAS-G12C inhibitor therapy, mainly due to intrinsic or acquired resistance caused by cellular, molecular, and genetic mechanisms. Improving the understanding of drug response in the tumor microenvironment may continue to promote the design, testing, and clinical application of KRAS-G12C inhibitors. 

摘要翻译： 

尽管长期以来被视为“不可成药”，但随着特异性结合KRAS-G12C突变蛋白的药物开发，直接抑制致癌RAS的临床试验近期取得了令人鼓舞的进展。特别是共价KRAS-G12C抑制剂sotorasib和adagrasib已被用于治疗携带KRAS-G12C突变的晚期非小细胞肺癌（NSCLC）患者。然而遗憾的是，绝大多数患者对KRAS-G12C抑制剂治疗无应答，这主要源于细胞、分子和遗传机制引起的固有或获得性耐药。深化对肿瘤微环境中药物应答机制的理解，或将持续推动KRAS-G12C抑制剂的设计、测试及临床应用。

原文链接：

The KRAS-G12C inhibitor: activity and resistance