The Role of Autophagy in Cancer: Therapeutic Implications
Top Cited Papers
- 1 September 2011
- journal article
- review article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 10 (9), 1533-1541
- https://doi.org/10.1158/1535-7163.mct-11-0047
Abstract
Autophagy is a homeostatic, catabolic degradation process whereby cellular proteins and organelles are engulfed by autophagosomes, digested in lysosomes, and recycled to sustain cellular metabolism. Autophagy has dual roles in cancer, acting as both a tumor suppressor by preventing the accumulation of damaged proteins and organelles and as a mechanism of cell survival that can promote the growth of established tumors. Tumor cells activate autophagy in response to cellular stress and/or increased metabolic demands related to rapid cell proliferation. Autophagy-related stress tolerance can enable cell survival by maintaining energy production that can lead to tumor growth and therapeutic resistance. As shown in preclinical models, inhibition of autophagy restored chemosensitivity and enhanced tumor cell death. These results established autophagy as a therapeutic target and led to multiple early phase clinical trials in humans to evaluate autophagy inhibition using hydroxychloroquine in combination with chemotherapy or targeted agents. Targeting autophagy in cancer will provide new opportunities for drug development, because more potent and specific inhibitors of autophagy are needed. The role of autophagy and its regulation in cancer cells continues to emerge, and studies aim to define optimal strategies to modulate autophagy for therapeutic advantage. Mol Cancer Ther; 10(9); 1533–41. ©2011 AACR.Keywords
This publication has 83 references indexed in Scilit:
- The role of the Atg1/ULK1 complex in autophagy regulationCurrent Opinion in Cell Biology, 2010
- Hypoxia-induced autophagy: cell death or cell survival?Current Opinion in Cell Biology, 2010
- HIF-1: upstream and downstream of cancer metabolismCurrent Opinion in Genetics & Development, 2010
- The IKK complex contributes to the induction of autophagyThe EMBO Journal, 2009
- Autophagy Suppresses Tumorigenesis through Elimination of p62Cell, 2009
- Cullin3-Based Polyubiquitination and p62-Dependent Aggregation of Caspase-8 Mediate Extrinsic Apoptosis SignalingCell, 2009
- Autophagy Inhibition Compromises Degradation of Ubiquitin-Proteasome Pathway SubstratesMolecular Cell, 2009
- A Molecule Targeting VHL-Deficient Renal Cell Carcinoma that Induces AutophagyCancer Cell, 2008
- Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesisCancer Cell, 2006
- ER Stress Regulation of ATF6 Localization by Dissociation of BiP/GRP78 Binding and Unmasking of Golgi Localization SignalsDevelopmental Cell, 2002