Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2020; 12(5): 303-322
Published online May 26, 2020. doi: 10.4252/wjsc.v12.i5.303
Molecular modulation of autophagy: New venture to target resistant cancer stem cells
Harpreet K Mandhair, Miroslav Arambasic, Urban Novak, Ramin Radpour
Harpreet K Mandhair, Miroslav Arambasic, Urban Novak, Ramin Radpour, Department for BioMedical Research, University of Bern, Bern 3008, Switzerland
Harpreet K Mandhair, Miroslav Arambasic, Urban Novak, Ramin Radpour, Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern 3008, Switzerland
Author contributions: Mandhair HK, Arambasic M, Novak U and Radpour R wrote the paper; Novak U and Radpour R are co-senior authors.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Ramin Radpour, MSc, PhD, Lecturer, Senior Researcher, Tumor Immunology, Department for BioMedical Research, University of Bern, Murtenstrasse 35, Bern 3008, Switzerland.
Received: February 27, 2020
Peer-review started: February 27, 2020
First decision: April 7, 2020
Revised: April 19, 2020
Accepted: May 5, 2020
Article in press: May 5, 2020
Published online: May 26, 2020

Autophagy is a highly regulated catabolic process in which superfluous, damaged organelles and other cytoplasmic constituents are delivered to the lysosome for clearance and the generation of macromolecule substrates during basal or stressed conditions. Autophagy is a bimodal process with a context dependent role in the initiation and the development of cancers. For instance, autophagy provides an adaptive response to cancer stem cells to survive metabolic stresses, by influencing disease propagation via modulation of essential signaling pathways or by promoting resistance to chemotherapeutics. Autophagy has been implicated in a cross talk with apoptosis. Understanding the complex interactions provides an opportunity to improve cancer therapy and the clinical outcome for the cancer patients. In this review, we provide a comprehensive view on the current knowledge on autophagy and its role in cancer cells with a particular focus on cancer stem cell homeostasis.

Keywords: Autophagy, Cancer stem cells, Cancer cells, Cancer therapy, Therapeutic resistance, Cancer metastasis

Core tip: Cancer stem cells (CSCs) are a distinct subpopulation in the tumor bulk that are highly plastic, and autophagy has been suggested to modulate their stemness and development during cancer progression. Autophagy is a pro-survival mechanism used by cancer cells to provide bioenergetic substrates. Therefore, dissecting the role of autophagy in cancer propagation can theoretically lead to a more efficient cancer treatment via the modulation of autophagy, in combination with chemotherapeutics to sensitize and target CSCs. This review summarizes the divergent role of autophagy in CSCs and cancer cells and attempts to elucidate the molecular mechanisms involved.