不太可能的靶向治疗:KRAS 作为非小细胞肺癌(NSCLC)的新兴靶点。
The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC).
机构信息
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
出版信息
Cell Rep Med. 2021 Jan 19;2(1):100186. doi: 10.1016/j.xcrm.2020.100186.
KRAS is a frequent oncogenic driver in solid tumors, including non-small cell lung cancer (NSCLC). It was previously thought to be an "undruggable" target due to the lack of deep binding pockets for specific small-molecule inhibitors. A better understanding of the mechanisms that drive KRAS transformation, improved KRAS-targeted drugs, and immunological approaches that aim at yielding immune responses against KRAS neoantigens have sparked a race for approved therapies. Few treatments are available for KRAS mutant NSCLC patients, and several approaches are being tested in clinicals trials to fill this void. Here, we review promising therapeutics tested for KRAS mutant NSCLC.
KRAS 是实体肿瘤中一种常见的致癌驱动基因,包括非小细胞肺癌(NSCLC)。由于缺乏针对特定小分子抑制剂的深结合口袋,此前它被认为是一个“不可成药”的靶点。对驱动 KRAS 转化的机制有了更好的理解,改进的 KRAS 靶向药物,以及旨在针对 KRAS 新抗原产生免疫反应的免疫方法,激发了对获批疗法的竞争。KRAS 突变型 NSCLC 患者的可用治疗方法很少,目前正在临床试验中测试几种方法来填补这一空白。在这里,我们综述了针对 KRAS 突变型 NSCLC 进行测试的有前途的治疗方法。