Paton Emily L, Turner Jacqueline A, Schlaepfer Isabel R
Division of Medical Oncology, The University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA.
J Oncol. 2020 Jan 3;2020:1079827. doi: 10.1155/2020/1079827. eCollection 2020.
Overactivation of the mitogen-activated protein kinase (MAPK) pathway is an important driver of many human cancers. First line, FDA-approved therapies targeting MAPK signalling, which include BRAF and MEK inhibitors, have variable success across cancers, and a significant number of patients quickly develop resistance. In recent years, a number of preclinical studies have reported alternative methods of overcoming resistance, which include promoting apoptosis, modulating autophagy, and targeting mitochondrial metabolism. This review summarizes mechanisms of resistance to approved MAPK-targeted therapies in BRAF-mutated cancers and discusses novel preclinical approaches to overcoming resistance.
丝裂原活化蛋白激酶（MAPK）信号通路的过度激活是许多人类癌症的重要驱动因素。一线经美国食品药品监督管理局（FDA）批准的针对MAPK信号传导的疗法，包括BRAF和MEK抑制剂，在不同癌症中的治疗效果各异，并且大量患者会迅速产生耐药性。近年来，多项临床前研究报告了克服耐药性的替代方法，包括促进细胞凋亡、调节自噬和靶向线粒体代谢。本综述总结了BRAF突变型癌症中对已批准的MAPK靶向疗法产生耐药性的机制，并讨论了克服耐药性的新临床前方法。
