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World J Gastroenterol. Nov 14, 2018; 24(42): 4738-4749
Published online Nov 14, 2018. doi: 10.3748/wjg.v24.i42.4738
CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer
Sara Cabrero-de las Heras, Eva Martínez-Balibrea
Sara Cabrero-de las Heras, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Germans Trias i Pujol health research institute (IGTP), Badalona, Barcelona 08916, Catalunya, Spain
Sara Cabrero-de las Heras, Program of Predictive and Personalized Cancer Medicine (PMPPC), Germans Trias i Pujol health research institute (IGTP), Badalona, Barcelona 08916, Catalunya, Spain
Author contributions: Both authors contributed equally to the conception and design of the study, literature review and analysis, drafting and critical revision and editing, and approval of the final version.
Supported by the Institute of Health Carlos III (ISCIII), No. PI16/01800 and PIE16/00011 (Co-funded by European Regional Development Fund "A way to make Europe").
Conflict-of-interest statement: The authors declare no potential conflicts of interest.
Open-Access: This 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 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/
Corresponding author: Eva Martinez-Balibrea, PhD, Senior Scientist, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Germans Trias i Pujol health research institute (IGTP), Carretera de Can Ruti, camí de les escoles s/n, Badalona, Barcelona 08916, Catalunya, Spain. embalibrea@iconcologia.net
Received: July 5, 2018
Peer-review started: July 5, 2018
First decision: August 25, 2018
Revised: September 27, 2018
Accepted: October 16, 2018
Article in press: October 16, 2018
Published online: November 14, 2018
Abstract

Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women, worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival rates. In metastatic patients, the use of predictive biomarkers could potentially result in more personalized treatments and better outcomes. The CXC family of chemokines (CXCL1 to 17) are small (8 to 10 kDa) secreted proteins that attract neutrophils and lymphocytes. These chemokines signal through chemokine receptors (CXCR) 1 to 8. Several studies have reported that these chemokines and receptors have a role in either the promotion or inhibition of cancer, depending on their capacity to suppress or stimulate the action of the immune system, respectively. In general terms, activation of the CXCR1/CXCR2 pathway or the CXCR4/CXCR7 pathway is associated with tumor aggressiveness and poor prognosis; therefore, the specific inhibition of these receptors is a possible therapeutic strategy. On the other hand, the lesser known CXCR3 and CXCR5 axes are generally considered to be tumor suppressor signaling pathways, and their stimulation has been suggested as a way to fight cancer. These pathways have been studied in tumor tissues (using immunohistochemistry or measuring mRNA levels) or serum [using enzyme-linked immuno sorbent assay (ELISA) or multiplexing techniques], among other sample types. Common variants in genes encoding for the CXC chemokines have also been investigated as possible biomarkers of the disease. This review summarizes the most recent findings on the role of CXC chemokines and their receptors in CRC and discusses their possible value as prognostic or predictive biomarkers as well as the possibility of targeting them as a therapeutic strategy.

Keywords: Colorectal cancer, CXC chemokines, Immune system, Biomarkers, Treatment, Chemotherapy, Oxaliplatin, Irinotecan, Immunotherapy, Bevacizumab

Core Tip: The contribution of the immune system to the development and progression of cancer is now fully acknowledged. The specific action of the immune system depends on the type of immune cells that are recruited to the tumor sites. Chemokines from the CXC subfamily are released by tumor cells and cells within the tumor microenvironment, whereupon they attract cells with anti-tumor (e.g., CD4⁺ and CD8⁺ lymphocytes) or pro-tumor activity (e.g., myeloid-derived suppressor cells). Chemokines have been proposed as prognostic factors, as biomarkers of response to therapy and as drug targets. The present review addresses the most recent findings in the field.