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World J Clin Cases. Aug 6, 2021; 9(22): 6234-6243
Published online Aug 6, 2021. doi: 10.12998/wjcc.v9.i22.6234
Role of autophagy in cholangiocarcinoma: Pathophysiology and implications for therapy
Elisabetta Ninfole, Claudio Pinto, Antonio Benedetti, Marco Marzioni, Luca Maroni
Elisabetta Ninfole, Claudio Pinto, Antonio Benedetti, Luca Maroni, Department of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona 60126, Italy
Marco Marzioni, Department of Gastroenterology, Università Politecnica delle Marche, Ancona 60126, Italy
Author contributions: Ninfole E wrote the manuscript; Benefetti A oversaw the manuscript preparation and writing; Pinto C contributed to writing of the manuscript; Marzioni M contributed to revision of the manuscript and the figures; Maroni L supervised and controlled the preparation of the manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Luca Maroni, MD, PhD, Research Associate, Department of Gastroenterology and Hepatology, Università Politecnica delle Marche, Via Tronto 10A, Ancona 60126, Italy. l.maroni@univpm.it
Received: February 18, 2021
Peer-review started: February 18, 2021
First decision: March 16, 2021
Revised: March 26, 2021
Accepted: June 28, 2021
Article in press: June 28, 2021
Published online: August 6, 2021
Processing time: 159 Days and 15.7 Hours
Abstract

Cholangiocarcinoma (CCA) is a malignant tumour of the biliary system that originates from the neoplastic transformation of cholangiocytes. CCA is characterized by late diagnosis and poor outcome, with surgery considered as the last option for management. Autophagy is a physiological lysosomal degradation process, essential for cellular homeostasis and ubiquitous in all eukaryotic cells. Several studies have reported a potential involvement of autophagy in cancer, but it remains unclear whether activation of this process represents a survival mechanism of cancer cells. In the present review, we examine the autophagic process and summarize the current knowledge about the involvement of autophagy in the progression of cancer. The link between autophagy and chemoresistance and the use of autophagic markers in diagnosis are also considered in detail. Preliminary evidence shows that the combination of autophagy modulators (activators or inhibitors) with conventional chemotherapeutic agents offers a possible treatment option against signalling pathways that are hyperactivated or altered in CCA. In vitro evidence suggests that combination of chemotherapy agents, such as cisplatin, under activation or inhibition of autophagic processes, in two different CCA cell lines, may improve chemosensitivity and reduce cell survival, respectively. A deeper understanding of these pathways, in both cancer and non-cancer cells, could unveil possible therapeutic targets to treat CCA patients.

Keywords: Cholangiocarcinoma; Cholangiocytes; Autophagy; Apoptosis; Chemoresistance; Autophagolysosome

Core Tip: This article reviews the occurrence and development of autophagy in cholangiocarcinoma and the corresponding therapeutic treatments. We analyse the role of autophagy in cancer, the link between autophagy and chemoresistance, and the use of autophagic markers in diagnostics. Overall, autophagy is a promising target in cancer therapy. Ongoing studies have the potential to unveil cancer-specific pathways amenable to therapeutic intervention.