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The Role of Autophagy in Cancer: From Molecular Mechanism to Therapeutic Window Publisher Pubmed



Jalali P1 ; Shahmoradi A2 ; Samii A3 ; Mazloomnejad R1 ; Hatamnejad MR4 ; Saeed A5 ; Namdar A6 ; Salehi Z7
Authors
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Authors Affiliations
  1. 1. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Department of Laboratory Medicine, Faculty of Paramedical, Kurdistan University of Medical Sciences, Sanandaj, Iran
  3. 3. Department of Hematology and Blood Transfusion, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
  5. 5. Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
  6. 6. Program in Cell Biology, The Hospital for Sick Children Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada
  7. 7. Department of Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran

Source: Frontiers in Immunology Published:2025


Abstract

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy and cancer is well-established; however, the biphasic nature of autophagy, acting as either a tumor growth inhibitor or promoter, has raised concerns regarding the regulation of tumorigenesis without inadvertently activating harmful aspects of autophagy. Consequently, elucidating the mechanisms by which autophagy contributes to cancer pathogenesis and the factors determining its pro- or anti-tumor effects is vital for devising effective therapeutic strategies. Furthermore, precision medicine approaches that tailor interventions to individual patients may enhance the efficacy of autophagy-related cancer treatments. To this end, interventions aimed at modulating the fate of tumor cells by controlling or inducing autophagy substrates necessitate meticulous monitoring of these mediators’ functions within the tumor microenvironment to make informed decisions regarding their activation or inactivation. This review provides an updated perspective on the roles of autophagy in cancer, and discusses the potential challenges associated with autophagy-related cancer treatment. The article also highlights currently available strategies and identifies questions that require further investigation in the future. Copyright © 2025 Jalali, Shahmoradi, Samii, Mazloomnejad, Hatamnejad, Saeed, Namdar and Salehi.
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