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  • Review Article
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Impact of context-dependent autophagy states on tumor progression

Nature Cancer volume 4, pages 596–607 (2023)Cite this article

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Abstract

Macroautophagy is a cellular quality-control process that degrades proteins, protein aggregates and damaged organelles. Autophagy plays a fundamental role in cancer where, in the presence of stressors (for example, nutrient starvation, hypoxia, mechanical pressure), tumor cells activate it to degrade intracellular substrates and provide energy. Cell-autonomous autophagy in tumor cells and cell-nonautonomous autophagy in the tumor microenvironment and in the host converge on mechanisms that modulate metabolic fitness, DNA integrity and immune escape and, consequently, support tumor growth. In this Review, we will discuss insights into the tumor-modulating roles of autophagy in different contexts and reflect on how future studies using physiological culture systems may help to understand the complexity and open new therapeutic avenues.

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Fig. 1: Molecular mechanisms of autophagy.
Fig. 2: Cellular responses modulating autophagy.
Fig. 3: Autophagy in the tumor and surrounding microenvironment.
Fig. 4: Autophagy in the tumor-bearing host.

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Acknowledgements

We apologize for the omission of any primary references. This work was supported by NCI grants P01CA117969, R35CA232124, P30CA016087-38 and 1R01CA251726-01A1, the Lustgarten Foundation and an SU2C grant to A.C.K.

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  1. Department of Radiation Oncology, New York University Langone Health, New York, NY, USA

    Mohamad Assi & Alec C. Kimmelman

  2. Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA

    Mohamad Assi & Alec C. Kimmelman

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Correspondence to Alec C. Kimmelman.

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Competing interests

A.C.K. has financial interests in Vescor Therapeutics and is an inventor on patents pertaining to KRAS-regulated metabolic pathways and redox control pathways in pancreatic cancer, targeting GOT1 as a therapeutic approach, targeting alanine transport and the autophagic control of iron metabolism. A.C.K. is on the scientific advisory board of Rafael/Cornerstone Pharmaceuticals, is an advisor for OncoRev and has been a consultant for Deciphera and AbbVie. The other author declares no competing interests. M.A. is postdoctoral fellow at New York University Langone Health.

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Assi, M., Kimmelman, A.C. Impact of context-dependent autophagy states on tumor progression. Nat Cancer 4, 596–607 (2023). https://doi.org/10.1038/s43018-023-00546-7

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