Evolutionarily conserved across eukaryotic cells, macroautophagy (herein autophagy) is an intracellular catabolic degradative process targeting damaged and superfluous cellular proteins, organelles, and other cytoplasmic components. Mechanistically, it involves formation of double-membrane vesicles called autophagosomes that capture cytosolic cargo and deliver it to lysosomes, wherein the breakdown products are eventually recycled back to the cytoplasm. Dysregulation of autophagy often results in various disease manifestations, including neurodegeneration, microbial infections, and cancer. In the case of cancer, extensive attention has been devoted to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion. In this review, while we summarize how this self-eating process is implicated at various stages of tumorigenesis, most importantly, we address the link between autophagy and hallmarks of cancer. This would eventually provide a better understanding of tumor dependence on autophagy. We also discuss how therapeutics targeting autophagy can counter various transformations involved in tumorigenesis. Finally, this review will provide a novel insight into the mutational landscapes of autophagy-related genes in several human cancers, using genetic information collected from an array of cancers.

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Shikha Satendra Singh and Somya Vats contributed equally to this work.


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APK was supported by grants from National Medical Research Council of Singapore, NCIS Yong Siew Yoon Research Grant through donations from the Yong Loo Lin Trust and by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence initiative to Cancer Science Institute of Singapore, National University of Singapore. This work was also supported by Wellcome Trust/DBT India Alliance Intermediate Fellowship (509159/Z/09/Z) and JNCASR intramural funds to RM. The JNCASR doctoral fellowship to SV is also acknowledged. We also thank Dr. Prathibha Ranganathan (Centre for Human Genetics, Bengaluru), Aparna Hebbar and members of Autophagy lab (JNCASR) for critical reading of the manuscript. This work was supported by NUHS Basic seed grant [T1-BSRG 2015-02] and Ministry of Education Tier 1 grant to GS. The John Nott Cancer Fellowship from Cancer Council, Western Australia also supported GS. This work is supported in part by National Medical Research Council Singapore (NMRC) grants (NMRC-CIRG/1346/2012 and NMRC/CIRG/1373/2013) to HMS.

Author information

Author notes


    1. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

      • Shikha Satendra Singh
      • , Tuan Zea Tan
      • , Boon Cher Goh
      • , Ruby Yun-Ju Huang
      •  & Alan Prem Kumar
    2. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

      • Shikha Satendra Singh
      • , Amelia Yi-Qian Chia
      • , Boon Cher Goh
      • , Gautam Sethi
      •  & Alan Prem Kumar
    3. Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, Karnataka, India

      • Somya Vats
      •  & Ravi Manjithaya
    4. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

      • Shuo Deng
      • , Mei Shan Ong
      • , Celestial T. Yap
      •  & Han Ming Shen
    5. Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia

      • Frank Arfuso
    6. Department of Haematology-Oncology, National University Hospital, National University Health System, Singapore, Singapore

      • Boon Cher Goh
    7. National University Cancer Institute, National University Health System, Singapore, Singapore

      • Boon Cher Goh
      •  & Alan Prem Kumar
    8. School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia

      • Gautam Sethi
    9. Department of Obstetrics and Gynaecology, National University Health System, Singapore, Singapore

      • Ruby Yun-Ju Huang
    10. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

      • Ruby Yun-Ju Huang
    11. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore

      • Han Ming Shen
    12. Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA, Australia

      • Alan Prem Kumar
    13. Medical Science Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

      • Alan Prem Kumar


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    Conflict of interest

    The authors declare that they have no competing interests.

    Corresponding authors

    Correspondence to Ravi Manjithaya or Alan Prem Kumar.

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