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Kondapuram et al. J Cancer Metastasis Treat 2019;5:32 Journal of Cancer
DOI: 10.20517/2394-4722.2018.105 Metastasis and Treatment

Review Open Access

Targeting autophagy with small molecules for cancer
therapy

Sree Karani Kondapuram , Sailu Sarvagalla , Mohane Selvaraj Coumar 1
2
1
1 Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
2 Division of Biology, Indian Institute of Science Education and Research (IISER)-Tirupati, Tirupati 517507, Andhra Pradesh, India.

Correspondence to: Dr. Mohane Selvaraj Coumar, Centre for Bioinformatics, School of Life Sciences, Pondicherry University,
Kalapet, Puducherry 605014, India. E-mail: mohane@bicpu.edu.in

How to cite this article: Kondapuram SK, Sarvagalla S, Coumar MS. Targeting autophagy with small molecules for cancer
therapy. J Cancer Metastasis Treat 2019;5:32. http://dx.doi.org/10.20517/2394-4722.2018.105

Received: 21 Dec 2018 First Decision: 7 Jan 2019 Revised: 18 Feb 2019 Accepted: 19 Feb 2019 Published: 19 Apr 2019

Science Editor: Chun Hei Antonio Cheung Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Autophagy is a conserved lysosomal-dependent catabolic process that maintains the cellular homeostasis by
recycling misfolded proteins and damaged organelles. It involves a series of ordered events (initiation, nucleation,
elongation, lysosomal fusion and degradation) that are tightly regulated/controlled by diverse cell signals and
stress. It is like a double-edged sword that can play either a protective or destructive role in cancer, by pro-survival
or apoptotic cues. Recently, modulating autophagy by pharmacological agents has become an attractive strategy
to treat cancer. Currently, a number of small molecules that inhibit autophagy initiation (e.g., ULK kinase inhibitors),
nucleation (e.g., Vps34 inhibitors), elongation (e.g., ATG4 inhibitors) and lysosome fusion (e.g., chloroquine, hydroxyl
chloroquine, etc.) are reported in pre-clinical and clinical study. Also a number of small molecules reported to induce
autophagy by targeting mammalian target of rapamycin (e.g., rapamycin analogs) or adenosine 5’-monophosphate-
activated protein kinase (e.g., sulforaphane). The study results suggest that many potential “druggable” targets exist
in the autophagy pathway that could be harnessed for developing new cancer therapeutics. In this review, we discuss
the reported autophagy modulators (inhibitors and inducers), their molecular mode of action and their applications
in cancer therapy.

Keywords: Autophagy, cancer, ATG, ULK inhibitor, Vps34 inhibitor, mammalian target of rapamycin inhibitors,
lysosome fusion inhibitors

INTRODUCTION
Autophagy is a natural cellular process that occurs for the maintenance of cellular homeostasis. During
autophagy, catabolic degradation occurs to recycle unnecessary, dysfunctional cellular components,

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
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