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Targeting autophagy in cancer
Open accessAbstract
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 (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]
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“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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Metadata
- Authors
- Levy, J. M. M., Towers, C. G., & Thorburn, A.
- Affiliations
- Morgan Adams Foundation (US)
- University of Colorado Anschutz (US)
- Corresponding author
- Thorburn, Andrew
- Venue
- Nature Reviews Cancer
- Published
- 2017-07-28
- Volume
- 17
- Issue
- 9
- Pages
- 528-542
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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