Targeting Autophagy in Cancer

Levy, Jean M. Mulcahy; Towers, Christina G.; Thorburn, Andrew

doi:10.1038/nrc.2017.53

Cited by 2,526Autophagy in Disease and TherapyCalcium signaling and nucleotide metabolismUbiquitin and proteasome pathways

Targeting Autophagy in Cancer

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Levy, Jean M. Mulcahy, Towers, Christina G., Thorburn, Andrew·2017·Nature Reviews Cancer

DOI 10.1038/nrc.2017.53PMC PMC5975367

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Abstract

Autophagy is a mechanism by which cellular material is delivered to lysosomes for degradation, leading to the basal turnover of cell components and providing energy and macromolecular precursors. Autophagy has opposing, context-dependent roles in cancer, and interventions to both stimulate and inhibit autophagy have been proposed as cancer therapies. This has led to the therapeutic targeting of autophagy in cancer to be sometimes viewed as controversial. In this Review, we suggest a way forwards for the effective targeting of autophagy by understanding the context-dependent roles of autophagy and by capitalizing on modern approaches to clinical trial design.

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Proficient autophagic responses most often mediate cytoprotective rather than cytotoxic effects in adaptation to stress.
“Proficient autophagic responses (which are under tight transcriptional and post-translational regulation) [509 799–805] most often operate at the hub of adaptation to stress, hence mediating cytoprotective (rather than cytotoxic) effects [806–811].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [807]
CQ and its derivative hydroxychloroquine are currently the only clinically available drugs to inhibit autophagy.
“CQ and its derivative hydroxychloroquine, a broadly used anti-malarial agent, are currently the only clinically available drugs to inhibit autophagy43.”
From AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields) (2018) · cites this paper as [43]

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[2]The Nobel Assembly The Nobel Assembly at Karolinska Instiutet has today decided to award the 2016 Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi < https://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/press.html> 2016

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Authors: Levy, J. M. M., Towers, C. G., & Thorburn, A.
Affiliations: Morgan Adams Foundation (US)
University of Colorado Anschutz (US)
Corresponding author: Thorburn, Andrew
ORCID: Levy, Jean M. Mulcahy
Towers, Christina G.
Thorburn, Andrew
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2017-07-28
Volume: 17
Issue: 9
Pages: 528-542
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc.2017.53
PMC: PMC5975367
OpenAlex: W2740618823
Cited by: 2,526
References: 141
Citations by year: 2026: 131 · 2025: 193 · 2024: 294 · 2023: 358 · 2022: 384 · 2021: 420 · 2020: 360 · 2019: 225 · 2018: 146 · 2017: 14
FWCI: 27.26
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Helmholtz Centre for Ocean Research Kiel (GEOMAR) (acceptedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA150925, K08CA193982, R01CA190170, R21CA197887, T32CA190216)
Topics: Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords: autophagy, cancer therapy, autophagy inhibition, lysosomal degradation, clinical trial design
MeSH terms: Sequestosome-1 Protein, Animals, Antineoplastic Agents, Autophagy, Chloroquine, Clinical Trials as Topic, Humans, Hydroxychloroquine, Microtubule-Associated Proteins, Neoplasms, Biomarkers, Tumor, Tumor Escape

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Targeting Autophagy in Cancer

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