Nyfeler Beat, Eng Christina H
a Department of Developmental and Molecular Pathways , Novartis Institutes for BioMedical Research , Basel , Switzerland.
b Oncology Research Unit , Pfizer , Pearl River , NY , USA.
Autophagy. 2016 Jul 2;12(7):1206-7. doi: 10.1080/15548627.2016.1170265. Epub 2016 Apr 20.
Inhibition of autophagy has been widely explored as a potential therapeutic intervention for cancer. Different factors such as tumor origin, tumor stage and genetic background can define a tumor's response to autophagy modulation. Notably, tumors with oncogenic mutations in KRAS were reported to depend on macroautophagy in order to cope with oncogene-induced metabolic stress. Our recent report details the unexpected finding that autophagy is dispensable for KRAS-driven tumor growth in vitro and in vivo. Additionally, we clarify that the antitumorigenic effects of chloroquine, a frequently used nonspecific inhibitor of autophagy, are not connected to the inhibition of macroautophagy. Our data suggest that caution should be exercised when using chloroquine and its analogs to decipher the roles of autophagy in cancer.
自噬抑制作为一种潜在的癌症治疗干预手段已得到广泛研究。肿瘤起源、肿瘤分期和基因背景等不同因素可决定肿瘤对自噬调节的反应。值得注意的是,据报道,具有KRAS致癌突变的肿瘤依赖巨自噬来应对致癌基因诱导的代谢应激。我们最近的报告详细阐述了一个意外发现,即自噬在体外和体内对KRAS驱动的肿瘤生长并非必需。此外,我们阐明了常用的非特异性自噬抑制剂氯喹的抗肿瘤作用与巨自噬抑制无关。我们的数据表明,在使用氯喹及其类似物来解读自噬在癌症中的作用时应谨慎。