Warnecke Brian, Nagasaka Misako
Department of Medicine, University of California Irvine School of Medicine, Chao Family Comprehensive Cancer Center, Orange, CA, USA.
Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Drug Des Devel Ther. 2024 Dec 5;18:5673-5683. doi: 10.2147/DDDT.S466217. eCollection 2024.
One of the most common mutations seen in lung cancers are mutations in Kristen Rat Sarcoma Viral Oncogene Homolog (KRAS), observed in 25-30% of patients with NSCLC. Mutations in KRAS result in oncogenesis via persistent activation of the MAPK/ERK pathways. Although once thought to be "undruggable", KRAS p.G12C inhibitors such as sotorasib and adagrasib have been developed. This paper focuses on adagrasib, the second KRAS p.G12C inhibitor to obtain regulatory approval by the FDA and describes the details on its study design, development and current place in therapy.
肺癌中最常见的突变之一是 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）的突变，在 25%至 30%的非小细胞肺癌患者中可观察到。KRAS 突变通过丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）通路的持续激活导致肿瘤发生。尽管 KRAS 曾被认为是“不可成药的”，但已开发出如索托拉西布和阿达格拉西布等 KRAS p.G12C 抑制剂。本文重点介绍阿达格拉西布，它是第二种获得美国食品药品监督管理局（FDA）监管批准的 KRAS p.G12C 抑制剂，并描述了其研究设计、研发情况及当前在治疗中的地位的详细信息。
