Experimental Murine Models for Colorectal Cancer Research

Abstract

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and in both sexes. Numerous animal models for CRC have been established to study its biology, namely carcinogen-induced models (CIMs) and genetically engineered mouse models (GEMMs). CIMs are valuable for assessing colitis-related carcinogenesis and studying chemoprevention. On the other hand, CRC GEMMs have proven to be useful for evaluating the tumor microenvironment and systemic immune responses, which have contributed to the discovery of novel therapeutic approaches. Although metastatic disease can be induced by orthotopic injection of CRC cell lines, the resulting models are not representative of the full genetic diversity of the disease due to the limited number of cell lines suitable for this purpose. On the other hand, patient-derived xenografts (PDX) are the most reliable for preclinical drug development due to their ability to retain pathological and molecular characteristics. In this review, the authors discuss the various murine CRC models with a focus on their clinical relevance, benefits, and drawbacks. From all models discussed, murine CRC models will continue to be an important tool in advancing our understanding and treatment of this disease, but additional research is required to find a model that can correctly reflect the pathophysiology of CRC.

Development of an in vivo syngeneic mouse transplant model of invasive intestinal adenocarcinoma driven by endogenous expression of Pik3caH1047R and Apc loss

“…Our model overcomes several drawbacks that hamper the utility of many murine models of colorectal cancer [ 7 , 8 , 16 – 18 ]. The subcutaneous transplantation approach facilitates monitoring and measuring of the tumour growth that is difficult with internal ( in situ ) gastrointestinal tumour models.…”

“…To facilitate translational research, it is essential to have appropriate preclinical models in which to test new therapeutic approaches. Typically, such models involve in vitro cell culture systems using human or mouse cancer cell lines [ 6 – 8 ]. More recently, three-dimensional organoid culture systems using primary patient-derived cells have become available [ 9 , 10 ].…”

“…To address this, many murine models of colorectal cancer have been reported, each with their own advantages and disadvantages [ 6 – 8 ]. Carcinogen-induced and genetically engineered models are perhaps the most physiologically relevant models, developing in situ and reproducing the early stages of oncogenesis.…”

The application of organoids in colorectal diseases

“…The 2D model can neither simulate tumors’ spatial structure and heterogeneity in vivo nor reflect the cell interactions in the CRC microenvironment. While PDX models can strongly simulate the structure, heterogeneity, and physiological environment of tumors, the immune-deficient mice used to create them lack normal immune function and cannot be used for tumor immunity-related research and drug development ( Neto et al, 2023 ). Unlike traditional models, organoid models derived from cancer tissues retain the molecular and biological characteristics of the malignant tissues ( Mao et al, 2023 ).…”