Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2020; 26(13): 1394-1426
Published online Apr 7, 2020. doi: 10.3748/wjg.v26.i13.1394
Mouse models of colorectal cancer: Past, present and future perspectives
Florian Bürtin, Christina S Mullins, Michael Linnebacher
Florian Bürtin, Department of General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, University of Rostock, Rostock 18057, Germany
Christina S Mullins, Department of Thoracic Surgery, University Medical Center Rostock, University of Rostock, Rostock 18057, Germany
Michael Linnebacher, Molecular Oncology and Immunotherapy, Department of General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, Rostock 18057, Germany
Author contributions: Linnebacher M was the main author involved in conception of the review including topics and angles addressed; Bürtin F performed the extensive PubMed search and drafted a first version; Mullins CS was the main author involved in manuscript editing including language editing; all authors participated in drafting the article and revising it critically for important intellectual content; and all authors gave their final approval of the submitted and revised version.
Supported by the State Mecklenburg-Vorpommern, No. TBI-V-1-241-VBW-084.
Conflict-of-interest statement: Dr. Linnebacher reports grants from Ministerium für Wirtschaft, Arbeit und Gesundheit Mecklenburg-Vorpommern during the conduct of the study.
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: Michael Linnebacher, PhD, Academic Fellow, Research Fellow, Research Scientist, Senior Researcher, Senior Scientist, Molecular Oncology and Immunotherapy, Department of General, Visceral, Vascular and Transplantation Surgery, University Medical Center Rostock, Schillingallee 69, Rostock 18057, Germany. michael.linnebacher@med.uni-rostock.de
Received: December 18, 2019
Peer-review started: December 18, 2019
First decision: February 18, 2020
Revised: March 5, 2020
Accepted: March 10, 2020
Article in press: March 10, 2020
Published online: April 7, 2020
Processing time: 111 Days and 1.1 Hours
Abstract

Colorectal cancer (CRC) is the third most common diagnosed malignancy among both sexes in the United States as well as in the European Union. While the incidence and mortality rates in western, high developed countries are declining, reflecting the success of screening programs and improved treatment regimen, a rise of the overall global CRC burden can be observed due to lifestyle changes paralleling an increasing human development index. Despite a growing insight into the biology of CRC and many therapeutic improvements in the recent decades, preclinical in vivo models are still indispensable for the development of new treatment approaches. Since the development of carcinogen-induced rodent models for CRC more than 80 years ago, a plethora of animal models has been established to study colon cancer biology. Despite tenuous invasiveness and metastatic behavior, these models are useful for chemoprevention studies and to evaluate colitis-related carcinogenesis. Genetically engineered mouse models (GEMM) mirror the pathogenesis of sporadic as well as inherited CRC depending on the specific molecular pathways activated or inhibited. Although the vast majority of CRC GEMM lack invasiveness, metastasis and tumor heterogeneity, they still have proven useful for examination of the tumor microenvironment as well as systemic immune responses; thus, supporting development of new therapeutic avenues. Induction of metastatic disease by orthotopic injection of CRC cell lines is possible, but the so generated models lack genetic diversity and the number of suited cell lines is very limited. Patient-derived xenografts, in contrast, maintain the pathological and molecular characteristics of the individual patient’s CRC after subcutaneous implantation into immunodeficient mice and are therefore most reliable for preclinical drug development – even in comparison to GEMM or cell line-based analyses. However, subcutaneous patient-derived xenograft models are less suitable for studying most aspects of the tumor microenvironment and anti-tumoral immune responses. The authors review the distinct mouse models of CRC with an emphasis on their clinical relevance and shed light on the latest developments in the field of preclinical CRC models.

Keywords: Colorectal cancer; Mouse models; Patient-derived xenografts; Carcinogen-induced models; Genetically engineered mouse models; Preclinical drug development

Core tip: This review highlights the different approaches to model colorectal cancer in the mouse. Carcinogen-induced rodent models, genetically engineered mouse models, heterotopic and orthotopic models as well as patient-derived xenografts are discussed with an emphasis on their specific advantages and disadvantages. Moreover, the historical background of animal models for cancer research and the future perspectives of colorectal cancer research are reviewed as well.