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Cited by 928Autophagy in Disease and TherapyCalcium signaling and nucleotide metabolismUbiquitin and proteasome pathways

Targeting Autophagy in Cancer: Recent Advances and Future Directions

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Amaravadi, Ravi K., Kimmelman, Alec C., Debnath, Jayanta·2019·Cancer Discovery
DOI 10.1158/2159-8290.cd-19-0292PMC PMC7306856
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Abstract

Autophagy, a multistep lysosomal degradation pathway that supports nutrient recycling and metabolic adaptation, has been implicated as a process that regulates cancer. Although autophagy induction may limit the development of tumors, evidence in mouse models demonstrates that autophagy inhibition can limit the growth of established tumors and improve response to cancer therapeutics. Certain cancer genotypes may be especially prone to autophagy inhibition. Different strategies for autophagy modulation may be needed depending on the cancer context. Here, we review new advances in the molecular control of autophagy, the role of selective autophagy in cancer, and the role of autophagy within the tumor microenvironment and tumor immunity. We also highlight clinical efforts to repurpose lysosomal inhibitors, such as hydroxychloroquine, as anticancer agents that block autophagy, as well as the development of more potent and specific autophagy inhibitors for cancer treatment, and review future directions for autophagy research.Significance: Autophagy plays a complex role in cancer, but autophagy inhibition may be an effective therapeutic strategy in advanced cancer. A deeper understanding of autophagy within the tumor microenvironment has enabled the development of novel inhibitors and clinical trial strategies. Challenges and opportunities remain to identify patients most likely to benefit from this approach.

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  • ALA-PDT induces autophagy.

    “Lastly, ALA-PDT is also known to induce autophagy, the degradation of cellular components by lysosomes.”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [37]

    Our copy describes autophagy as lysosomal degradation in “Bulk Degradation and Selective Autophagy Can Both Affect the Cancer Phenotype” (page unavailable), but it does not address whether ALA-PDT induces it. Searches for “ALA-PDT,” “photodynamic,” and “5-aminolevulinic acid” found no passage establishing that relationship. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Amaravadi, R. K., Kimmelman, A. C., & Debnath, J.
Affiliations
  • University of Pennsylvania (US)
  • NYU Langone’s Laura and Isaac Perlmutter Cancer Center (US)
  • University of California, San Francisco (US)
Corresponding author
Amaravadi, Ravi K.
ORCID
Venue
Cancer Discovery
Publisher
American Association for Cancer Research (AACR)
Published
2019-09-01
Volume
9
Issue
9
Pages
1167-1181
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
DOI
10.1158/2159-8290.cd-19-0292
PMC
PMC7306856
OpenAlex
W2969538494
Cited by
928
References
28
Citations by year
2026: 71 · 2025: 103 · 2024: 149 · 2023: 148 · 2022: 190 · 2021: 177 · 2020: 79 · 2019: 10
FWCI
16.85
Type
journal article
Language
en
Open access
Locations
  • Cancer Discovery (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NCI (P01CA114046, P30 CA016520, SPORE P50 CA174523, 1R01CA198015, R01CA157490, R01CA188048, P01CA117969, R35CA232124)
  • NIH (R01GM095567)
  • Lustgarten Foundation (R01CA201849, R01CA126792, R01CA213775)
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, autophagy inhibition, selective autophagy, tumor microenvironment, antitumor immunity, lysosomal inhibitors, hydroxychloroquine, autophagy inhibitors, cancer metabolism, nutrient cycling, autophagy modulation
MeSH terms
Animals, Antineoplastic Agents, Autophagy, Clinical Trials as Topic, Genotype, Humans, Neoplasms, Tumor Escape, Gene Regulatory Networks, Molecular Targeted Therapy, Tumor Microenvironment

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