Article Search

Journal of Cancer Prevention


J Cancer Prev 2022; 27(1): 1-6

Published online March 30, 2022

© Korean Society of Cancer Prevention

Genetic Alterations and Microenvironment that Drive Malignant Progression of Colorectal Cancer: Lessons from Mouse and Organoid Models

Mizuho Nakayama1,2 , Dong Wang1,2 , Sau Yee Kok1,3 , Hiroko Oshima1,2 , Masanobu Oshima1,2

1Division of Genetics, Cancer Research Institute, Kanazawa University, 2WPI Nano-Life Science Institute (Nano-LSI), Kanazawa University, Kanazawa, Japan, 3Cancer Immunology and Immunotherapy Unit, Cancer Research Malaysia, Selangor, Malaysia

Correspondence to :
Masanobu Oshima, E-mail:,

Received: January 10, 2022; Revised: February 13, 2022; Accepted: February 25, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Comprehensive genome analyses have identified frequently mutated genes in human colorectal cancers (CRC). These include APC, KRAS, SMAD4, TP53, and FBXW7. The biological functions of the respective gene products in cell proliferation and homeostasis have been intensively examined by in vitro experiments. However, how each gene mutation or combinations of specific mutations drive malignant progression of CRC in vivo has not been fully understood. Based on the genomic information, we generated mouse models that carry multiple mutations of CRC driver genes in various combinations, and we performed comprehensive histological analyses to link genetic alteration(s) and tumor phenotypes, including liver metastasis. In this review article, we summarize the phenotypes of the respective genetic models carrying major driver mutations and discuss a possible mechanism of mutations underlying malignant progression.

Keywords: Transgenic mice, Organoid, Colorectal cancer, Mutations, Elastic modulus

Share this article on :

Related articles in JCP

Most KeyWord