Cellular Mechanisms of Autophagy in Carcinogenesis: A Narrative Review

Year : 2026 | Volume : 15 | Issue : 01 | Page : 23 28
    By

    Sharique Ahmad,

  • Shekhar Srivastava,

  • Raushan Kumar,

  • Pooja Srivastav,

  • Pushpendra D. Pratap,

  • Faiza Hasan Khan,

  1. Professor, Department of Pathology, Era’s Lucknow Medical College & Hospital, Era University, Lucknowq, Uttar Pradesh, India
  2. Researcher, Department of Community Medicine, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
  3. Research Analyst, Department of Pathology, Era’s Lucknow Medical College and Hospital, Era University, Sarfarazganj, Hardoi Road, Lucknow, Uttar Pradesh, India
  4. Junior Resident, Department of Pathology, Era’s Lucknow Medical College & Hospital, Era University, Lucknow, Uttar Pradesh, India
  5. Research Analyst, Department of Research Metabolic Unit, Research Metabolic Unit, Era’s Lucknow Medical College & Hospital, Era University, Lucknow, Uttar Pradesh, India
  6. Researcher, Department of Pathology, Era’s Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India

Abstract

Autophagy is a highly conserved lysosomal degradation pathway essential for cellular homeostasis, metabolic adaptation, and survival under stress. In the context of carcinogenesis, autophagy exhibits a paradoxical and stage-dependent role. During early tumor development, autophagy acts as a tumor-suppressive mechanism by limiting genomic instability, oxidative stress, and chronic inflammation. Conversely, in established malignancies, cancer cells exploit autophagy to sustain growth, survive hostile tumor microenvironments, and resist anticancer therapies. Increasing evidence highlights the relevance of autophagy not only as a biological process but also as a diagnostic, prognostic, and predictive biomarker in oncology and pathology. This review comprehensively examines the cellular and molecular mechanisms of autophagy in carcinogenesis, highlighting how autophagy functions as a dynamic and context-dependent biological process during tumor initiation, progression, and metastasis. Emphasis is placed on tumor-specific patterns of autophagic activity across different cancer types and the role of commonly used immunohistochemical markers, such as LC3, Beclin-1, and p62, in evaluating autophagic flux within tissue specimens. The review also discusses the interaction of autophagy with apoptosis, cellular metabolism, hypoxia, and immune modulation within the tumor microenvironment. Furthermore, its diagnostic, prognostic, and therapeutic implications are explored, including resistance to chemotherapy and radiotherapy. Understanding the dual and sometimes paradoxical nature of autophagy – as both a tumor-suppressive and tumor-promoting process – is essential for the rational design and clinical application of autophagy-targeted therapeutic strategies in cancer management.

Keywords: Autophagy, beclin-1, cancer therapy, carcinogenesis, immunohistochemistry, LC3, p62, tumor biology

[This article belongs to Research and Reviews: Journal of Oncology and Hematology ]

How to cite this article:
Sharique Ahmad, Shekhar Srivastava, Raushan Kumar, Pooja Srivastav, Pushpendra D. Pratap, Faiza Hasan Khan. Cellular Mechanisms of Autophagy in Carcinogenesis: A Narrative Review. Research and Reviews: Journal of Oncology and Hematology. 2026; 15(01):23-28.
How to cite this URL:
Sharique Ahmad, Shekhar Srivastava, Raushan Kumar, Pooja Srivastav, Pushpendra D. Pratap, Faiza Hasan Khan. Cellular Mechanisms of Autophagy in Carcinogenesis: A Narrative Review. Research and Reviews: Journal of Oncology and Hematology. 2026; 15(01):23-28. Available from: https://journals.stmjournals.com/rrjooh/article=2026/view=239157


References

  1. Mizushima N, Komatsu M. Autophagy: Renovation of cells and tissues. Cell. 2011;147(4):728–741.
  2. White E. The role for autophagy in cancer. J Clin Invest. 2015 Jan;125(1):42–46. doi:10.1172/JCI73941. PMID: 25654549; PMCID: PMC4382247.
  3. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27–42.
  4. Kim J, Guan KL. mTOR as a central hub of nutrient signalling and cell growth. Nat Cell Biol. 2019;21(1):63–71.
  5. Hardie DG. AMP-activated protein kinase: Maintaining energy homeostasis at the cellular and whole-body levels. Nat Rev Mol Cell Biol. 2012;13(4):251–262.
  6. Huang K, Fingar DC. Growing knowledge of the mTOR signaling network. InSeminars in cell & developmental biology 2014 Dec 1 (Vol. 36, pp. 79-90). Academic Press.
  7. Amaravadi RK, Kimmelman AC, White E. Targeting autophagy in cancer: recent advances and future directions. Cancer Discov. 2016;6(4):335–345. doi:10.1158/2159-8290.CD-15-1352. PMID: 26969630.
  8. Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, et al. Promotion of tumourigenesis by heterozygous disruption of the Beclin 1 autophagy gene. J Clin Invest. 2003;112(12):1809–1820.
  9. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122(6):927–939.
  10. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Atg8, is localized in autophagosome membranes after processing. EMBO J. 2000;19(21):5720–5728.
  11. Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY, et al. Autophagy suppresses tumourigenesis through elimination of p62. Cell. 2009;137(6):1062–1075.
  12. Nakamura S, Yoshimori T. New insights into autophagosome–lysosome fusion. J Cell Sci. 2017;130(7):1209–1216.
  13. Green DR, Galluzzi L. Mitochondria and the autophagy–inflammation–cancer axis. Science. 2014;345(6203):1250256.
  14. Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, et al. Molecular definitions of autophagy and related processes. EMBO J. 2017;36(13):1811–1836.
  15. Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S, et al. Autophagy-deficient mice develop multiple liver tumours. J Clin Invest. 2011;121(4):1276–1285.
  16. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumourigenesis by Beclin 1. Oncogene. 1999;18(45):5932–5940.
  17. Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer. 2017 Sep;17(9):528–542. doi:10.1038/nrc.2017.53. PMID: 28751651.
  18. Lock R, Roy S, Kenific CM, Su JS, Salas E, Ronen SM, et al. Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell. 2011 Feb 1;22(2):165–178. doi:10.1091/mbc.E10-06-0500. PMID: 21119005.
  19. Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouysségur J, et al. Hypoxia-induced autophagy is mediated through HIF-1α induction of BNIP3 and BNIP3L. Cell Cycle. 2009;8(21):3326–3332.
  20. Mulcahy Levy JM, Thorburn A. Targeting autophagy during cancer therapy to improve clinical outcomes. Pharmacol Ther. 2011;131(1):130–141. doi:10.1016/j.pharmthera.2011.03.009.
  21. Kenific CM, Debnath J. Cellular and metabolic functions for autophagy in cancer cells. Trends Cell Biol. 2015;25(1):37–45.
  22. Amaravadi RK, Kimmelman AC, White E. Recent insights into the function of autophagy in cancer. Clin Cancer Res. 2019;25(8):2184–2189.
  23. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021;17(1):1–382.
  24. Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 2006;10(1):51–64. doi:10.1016/j.ccr.2006.06.001.
  25. Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, et al. Autophagy in malignant transformation and cancer progression. Nat Rev Cancer. 2015;15(7):431–448.
  26. Kimmelman AC, White E. Autophagy and tumour metabolism. Genes Dev. 2017;31(12):1142–1155.
  27. Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumourigenesis. Genes Dev. 2011;25(5):460–470.
  28. Mauthe M, Orhon I, Rocchi C, Zhou X, Luhr M, Hijlkema KJ, et al. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy. 2018;14(8):1435–1455.
  29. Hassan AMIA, Zhao Y, Chen X, He C. Blockage of autophagy for cancer therapy: a comprehensive review. Int J Mol Sci. 2024;25(13):7459. doi:10.3390/ijms25137459.
  30. Rebecca VW, Amaravadi RK. Emerging strategies to effectively target autophagy in cancer. Oncogene. 2016;35(1):1–11.
  31. Rangwala R, Leone R, Chang YC, Fecher LA, Schuchter LM, Kramer A, et al. Phase I trial of hydroxychloroquine with chemotherapy in solid tumours. Clin Cancer Res. 2014;20(19):5038–5047.
  32. Egan DF, Chun MG, Vamos M, Zou H, Rong J, Miller CJ, et al. Small molecule inhibition of the autophagy kinase ULK1. Nat Chem Biol. 2015;11(10):778–785.
  33. Dowdle WE, Nyfeler B, Nagel J, Elling RA, Liu S, Triantafellow E, et al. Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4-mediated ferritinophagy. Nat Cell Biol. 2014;16(11):1069–1079.
  34. Pietrocola F, Bravo-San Pedro JM, Galluzzi L, Kroemer G. Autophagy in natural and therapy-driven anticancer immunosurveillance. Autophagy. 2017;13(12):2163–2170.
  35. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168(6):960–976.
  36. Galluzzi L, Bravo-San Pedro JM, Levine B, Green DR, Kroemer G. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017;16(7):487–511. doi:10.1038/nrd.2017.22.
  37. Towers CG, Thorburn A. Therapeutic targeting of autophagy. Nat Rev Cancer. 2016;16(5):307–320.
  38. Mulcahy Levy JM, Thorburn A. Autophagy in cancer: moving from understanding mechanism to improving therapy responses in patients. Cell Death Differ. 2020;27(3):843–857. doi:10.1038/s41418-019-0474-7.
Regular Issue Subscription Review Article
Volume 15
Issue 01
Received 07/02/2026
Accepted 09/02/2026
Published 23/03/2026
Publication Time 44 Days
26

Login


My IP

PlumX Metrics