Revisiting autophagy addiction of tumor cells.
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.
a Department of Developmental and Molecular Pathways , Novartis Institutes for BioMedical Research , Basel , Switzerland.
Beat
B
Nyfeler
b Oncology Research Unit , Pfizer , Pearl River , NY , USA.
Christina H
CH
Eng
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology*; D006801:Humans; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*
D018501:Antirheumatic Agents; C117307:KRAS protein, human; D002738:Chloroquine; D016283:Proto-Oncogene Proteins p21(ras)
ATG7; KRAS; autophagy; cancer; chloroquine