Zhao Hongyun, Zheng Bin
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Trends Cancer. 2019 Jun;5(6):327-329. doi: 10.1016/j.trecan.2019.04.003. Epub 2019 May 7.
In two recent articles, Kinsey et al. (Nature Medicine 2019;25:620-627) and Bryant et al. (Nature Medicine 2019;25:628-640) reported that inhibition of MEK-ERK signaling in KRAS-mutated cancers induced autophagic flux, presumably as a metabolic adaptation mechanism. Importantly, they demonstrated that autophagy blockade via chloroquine (CQ) or hydroxychloroquine (HCQ) enhanced the efficacy of MEK-ERK inhibition in various preclinical models of KRAS-driven cancers, providing a rational basis for future clinical evaluation of this combination therapy.
在最近的两篇文章中，金赛等人（《自然医学》2019年；25:620 - 627）和布赖恩特等人（《自然医学》2019年；25:628 - 640）报道，在KRAS突变型癌症中抑制MEK - ERK信号传导可诱导自噬通量，推测这是一种代谢适应机制。重要的是，他们证明，在各种KRAS驱动的癌症临床前模型中，通过氯喹（CQ）或羟氯喹（HCQ）阻断自噬可增强MEK - ERK抑制的疗效，为这种联合疗法未来的临床评估提供了合理依据。
