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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2017; 23(46): 8109-8119
Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8109
Relation of the IGF/IGF1R system to autophagy in colitis and colorectal cancer
Ferenc Sipos, Hajnal Székely, Imre Dániel Kis, Zsolt Tulassay, Györgyi Műzes
Ferenc Sipos, Hajnal Székely, Györgyi Műzes, 2nd Department of Internal Medicine, Semmelweis University, Budapest 1088, Hungary
Imre Dániel Kis, Faculty of Medicine, Semmelweis University, Budapest 1088, Hungary
Zsolt Tulassay, Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest 1088, Hungary
Author contributions: Sipos F, Székely H and Műzes G substantially contributed to the writing, editing and revision of the manuscript, and approved the final version of the article to be published; Sipos F and Székely H contributed equally to the writing of the manuscipt; Kis ID contributed in revising the paper and figure editing; Tulassay Z revised the final version of the manuscript.
Supported by the Hungarian Scientific Research Fund (No.OTKA-K111743) to Tulassay Z. The funders had no role in data collection, decision to publish, or preparation of the manuscript.
Conflict-of-interest statement: No conflict of interest.
Open-Access: 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/
Correspondence to: Ferens Sipos, MD, PhD, Assistant Professor, Immunology and Medicine, 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi street 46, Budapest 1088, Hungary. dr.siposf@gmail.com
Telephone: +36-1-266926-55622 Fax: +36-1-266926-55622
Received: October 27, 2017
Peer-review started: October 28, 2017
First decision: November 21, 2017
Revised: October 28, 2017
Accepted: December 4, 2017
Article in press: December 4, 2017
Published online: December 14, 2017
Abstract

Metabolic syndrome (MetS), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation is affected by the insulin-like growth factor 1 receptor (IGF1R) signaling pathway. The IGF1R pathway has been reported to regulate autophagy, as well, but sometimes through a bidirectional context. Targeting the IGF1R-autophagy crosstalk could represent a promising strategy for the development of new antiinflammatory and anticancer therapies, and may help for subjects suffering from MetS who are at increased risk of colorectal cancer. However, therapeutic responses to targeted therapies are often shortlived, since a signaling crosstalk of IGF1R with other receptor tyrosine kinases or autophagy exists, leading to acquired cellular resistance to therapy. From a pharmacological point of view, it is attractive to speculate that synergistic benefits could be achieved by inhibition of one of the key effectors of the IGF1R pathway, in parallel with the pharmacological stimulation of the autophagy machinery, but cautiousness is also required, because pharmacologic IGF1R modulation can initiate additional, sometimes unfavorable biologic effects.

Keywords: Insulin-like growth factor, IGF1R, Autophagy, Colitis, Colorectal cancer, Metabolic syndrome

Core tip: Targeting the insulin-like growth factor 1 receptor (IGF1R)-autophagy crosstalk could represent a promising strategy for the development of new antiinflammatory and anticancer therapies, and may help for subjects suffering from metabolic syndrome who are at increased risk of colorectal cancer. However, cautiousness is also required, because pharmacologic IGF1R modulation can initiate additional, sometimes unfavorable biologic effects.