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Updated: Mar 22, 2026

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Published on: January 31, 2025
Revisiting autophagy addiction of tumor cells
Beat Nyfeler1, Christina H Eng2
1a Department of Developmental and Molecular Pathways , Novartis Institutes for BioMedical Research , Basel , Switzerland.
Abstract:
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.
Insights
Autophagy is not essential for KRAS-driven tumors, contrary to previous beliefs. The study also found that chloroquine
Area of Science:
- Oncology
- Cell Biology
- Cancer Therapeutics
Background:
- Autophagy inhibition is a studied cancer therapy.
- Tumor characteristics influence autophagy response.
- KRAS-mutated tumors were thought to rely on autophagy for metabolic stress.
Purpose of the Study:
- To investigate the role of autophagy in KRAS-driven tumors.
- To determine if autophagy is essential for KRAS-driven tumor growth.
- To clarify the mechanism of chloroquine's anti-tumor effects.
Main Methods:
- In vitro and in vivo experiments.
- Genetic manipulation to inhibit autophagy.
- Treatment with chloroquine.
Main Results:
- Autophagy is dispensable for KRAS-driven tumor growth.
- Chloroquine's anti-tumor effects are independent of autophagy inhibition.
- KRAS-driven tumors do not rely on macroautophagy.
Conclusions:
- Autophagy is not required for KRAS-driven tumor progression.
- Chloroquine's therapeutic effects in cancer are not mediated by autophagy inhibition.
- Caution is advised when using chloroquine to study autophagy in cancer.
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