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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2016; 22(2): 490-500
Published online Jan 14, 2016. doi: 10.3748/wjg.v22.i2.490
Tropomyosin-related kinase B/brain derived-neurotrophic factor signaling pathway as a potential therapeutic target for colorectal cancer
Hussein Akil, Aurélie Perraud, Marie-Odile Jauberteau, Muriel Mathonnet
Hussein Akil, Aurélie Perraud, Marie-Odile Jauberteau, Muriel Mathonnet, Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA3842), Faculté de Médecine et de Pharmacie, Fédération de Recherche GEIST, 87025 Limoges, France
Aurélie Perraud, Muriel Mathonnet, Service de Chirurgie Digestive, Générale et Endocrinienne, CHU de Limoges, 87042 Limoges, France
Marie-Odile Jauberteau, Service d’Immunologie, CHU de Limoges, 87042 Limoges, France
Author contributions: Akil H wrote and designed the paper; Jauberteau MO and Mathonnet M contributed equally to this work; and Akil H, Perraud A, Jauberteau MO and Mathonnet M contributed to conception, critical revision and final approval of the manuscript.
Supported by Conseil Régional du Limousin and the CORC Comité Orientation Recherche Cancer.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
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: Hussein Akil, PhD, Laboratoire Homéostasie Cellulaire et Pathologies (LHCP-EA3842), Faculté de Médecine et de Pharmacie, Fédération de Recherche GEIST, Université de Limoges, 2 rue du Dr Marcland, 87025 Limoges, France. hussein.akil@outlook.fr
Telephone: +33-555-435868 Fax: +33-555-435916
Received: April 25, 2015
Peer-review started: April 27, 2015
First decision: September 11, 2015
Revised: September 25, 2015
Accepted: October 12, 2015
Article in press: October 13, 2015
Published online: January 14, 2016
Processing time: 255 Days and 23.3 Hours
Abstract

Colorectal cancer (CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients’ long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor (EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B (TrkB), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of TrkB and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating TrkB-expressing CRC tumors.

Keywords: Colorectal cancer; Tyrosine kinase receptor B; Brain-derived neurotrophic factor; Therapeutic targets; Cell survival

Core tip: Recently, the tropomyosin-related kinase B (TrkB)/brain derived-neurotrophic factor (BDNF) signaling pathway has emerged as a key player in the pathogenesis and prognosis of several non-neural cancers. Indeed, the TrkB tyrosine kinase receptor has been recently found to play an important role in the biological and clinical behavior of colorectal cancer (CRC). Here, we review the implications of TrkB and its ligand BDNF in CRC. Additionally, we discuss possible therapeutic strategies targeting this pathway.