The Double-edged Sword of Autophagy Modulation in Cancer

By E. White, Robert S. DiPaola. Clinical Cancer Research, 2009

1,126 citations recorded by the source corpus.

Macroautophagy (autophagy) is a lysosomal degradation pathway for the breakdown of intracellular proteins and organelles. Although constitutive autophagy is a homeostatic mechanism for intracellular recycling and metabolic regulation, autophagy is also stress responsive, in which it is important for the removal of damaged proteins and organelles. Autophagy thereby confers stress tolerance, limits damage, and sustains viability under adverse conditions. Autophagy is a tumor-suppression mechanism, yet it enables tumor cell survival in stress. Reconciling how loss of a prosurvival function can promote tumorigenesis, emerging evidence suggests that preservation of cellular fitness by autophagy may be key to tumor suppression. As autophagy is such a fundamental process, establishing how the functional status of autophagy influences tumorigenesis and treatment response is important. This is especially critical as many current cancer therapeutics activate autophagy. Therefore, efforts to understand and modulate the autophagy pathway will provide new approaches to cancer therapy and prevention. (Clin Cancer Res 2009;15(17):5308–16)

Subfields: Cell Biology, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/f71bc7c608b1265d54e3edb9fb6505f9860a5319

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In Cell Biology

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Citations in the corpus

• The Role of Autophagy in Cancer: Therapeutic Implications (2011, background): “Knockdown of essential autophagy genes in tumor cells has been shown to confer or potentiate the induction of cell death (7).”
• Autophagy as a target for anticancer therapy (2011, background): “Changes in the way cells respond to metabolic stress were proposed to be key factors in tumorigenesis”
• Pancreatic cancers require autophagy for tumor growth. (2011, neutral): “In line with the contextual pro-and anti-survival effects in normal cellular metabolism, the role of autophagy in cancer is also complex, with associations with both tumor suppression and therapeutic resistance in advanced tumors (Liang et al. 1999; White and DiPaola 2009).”
• Hallmarks of cancer: the next generation. (2011, neutral): “Perhaps paradoxically, nutrient starvation, radiotherapy, and certain cytotoxic drugs can induce elevated levels of autophagy that are apparently cytoprotective for cancer cells, impairing rather than accentuating the killing actions of these stressinducing situations (White and DiPaola, 2009; Apel ”
• Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review (2012, background): “In normal cells, autophagy stimulators may be useful for cancer prevention by enhancing damage mitigation and senescence, while autophagy inhibitors can induce tumorigenesis (White & DiPaola, 2009; Ravikumar et al., 2010; Chen & Karantza, 2011).”
• Autophagy and autophagy-related proteins in cancer (2020, background): “The potential ability of autophagy to modulate cell death makes it a therapeutic target in cancer [25, 26].”
• The Roles of Autophagy in Cancer (2018, background): “Suppression of autophagy by deletion of Beclin 1 enhances cell death [73,74].”
• Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity (2012, background): “In agreement, the monoallelic knock-out of Beclin-1 in mice enhances susceptibility to cancer [68,69].”