Koustas E, Trifylli EM, Sarantis P, Papavassiliou AG, Karamouzis MV. Role of autophagy in cholangiocarcinoma: An autophagy-based treatment strategy. World J Gastrointest Oncol 2021; 13(10): 1229-1243 [PMID: 34721764 DOI: 10.4251/wjgo.v13.i10.1229]
Corresponding Author of This Article
Evangelos Koustas, MD, PhD, Academic Research, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece. vang.koustas@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastrointest Oncol. Oct 15, 2021; 13(10): 1229-1243 Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1229
Role of autophagy in cholangiocarcinoma: An autophagy-based treatment strategy
Evangelos Koustas, Eleni-Myrto Trifylli, Panagiotis Sarantis, Athanasios G Papavassiliou, Michalis V Karamouzis
Evangelos Koustas, Eleni-Myrto Trifylli, Panagiotis Sarantis, Athanasios G Papavassiliou, Michalis V Karamouzis, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
Author contributions: All the authors made substantial contributions to the conception and design of the study, analysis and interpretation of data; Also, drafted the article, made critical revisions and gave the final approval of the version of the article to be published.
Conflict-of-interest statement: The 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Evangelos Koustas, MD, PhD, Academic Research, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, 11527, Athens, Greece. vang.koustas@gmail.com
Received: February 21, 2021 Peer-review started: February 21, 2021 First decision: April 19, 2021 Revised: April 28, 2021 Accepted: August 3, 2021 Article in press: August 3, 2021 Published online: October 15, 2021 Processing time: 233 Days and 20.6 Hours
Abstract
Cholangiocarcinomas (CCAs) are diverse biliary epithelial tumours involving the intrahepatic, perihilar and distal parts of the biliary tree. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis and strategy for clinical management. However, many cholangiocarcinoma tumor-cells appear to be resistant to current chemotherapeutic agents. The role of autophagy and the therapeutic value of autophagy-based therapy are largely unknown in CCA. The multistep nature of autophagy offers a plethora of regulation points, which are prone to be deregulated and cause different human diseases, including cancer. However, it offers multiple targetable points for designing novel therapeutic strategies. Tumor cells have evolved to use autophagy as an adaptive mechanism for survival under stressful conditions such as energy imbalance and hypoxic region of tumors within the tumor microenvironment, but also to increase invasiveness and resistance to chemotherapy. The purpose of this review is to summarize the current knowledge regarding the interplay between autophagy and cholangiocarcinogenesis, together with some preclinical studies with agents that modulate autophagy in order to induce tumor cell death. Altogether, a combinatorial strategy, which comprises the current anti-cancer agents and autophagy modulators, would represent a positive CCA patient approach.
Core Tip: The significant role of autophagy in maintaining the energy balance of cancer cells in tumorigenesis remains controversial. A grown body of research data suggests that autophagy is a promising target for several cancer types, including cholangiocarcinomas (CCAs). A novel therapeutic approach which could involve autophagy manipulation plus chemotherapeutic agents may open a new field for more beneficial therapeutic strategies for patients with CCA.
