Figure 1.

Mouse models of advanced colorectal cancer (CRC) as research and preclinical tools. The development of genetically engineered mouse models (GEMMs) carrying gene mutations that closely match those found by deep‐sequencing of human colorectal carcinomas provide information on the homeostatic and tumourigenic role of a gene in the intestine. Orthotopic transplantation of select colorectal carcinoma cell lines to the caecum of immune‐deficient mice results in primary tumour growth and metastases to lymph nodes or liver. Prior to transplantation, colorectal carcinoma cell lines can be genetically manipulated to overexpress (cDNA vector) or inhibit (shRNA or CRISPR‐Cas9 vector) a gene of interest to rapidly assess its biological role or to validate potential therapeutic targets. Introducing a reporter gene, such as green fluorescent protein (GFP), to cells prior to transplantation allows in vivo monitoring of primary tumour or metastases growth, which is extremely useful when assessing responses to pharmacological agents or inducible genetic manipulation. Single‐cell suspensions from carcinomas can be flow‐sorted using cell‐specific markers to identify cells of interest, for example stem‐like cells for growth of organoids, or to gain further insight into the tumour cells of origin and their interactions with the microenvironment. Cultured cells can be utilised for drug sensitivity screens. Mouse models of advanced CRC can be used to screen for cancer driver genes and disease biomarkers.