Capturing cancer evolution using genetically engineered mouse models (GEMMs)

Initiating from a single cell, cancer undergoes clonal evolution, leading to a high degree of intratumor heterogeneity (ITH). The arising genetic heterogeneity between cancer cells is influenced by exogenous and endogenous forces that shape the composition of clones within tumors. Preclinical mouse models have provided a valuable tool for understanding cancer, helping to build a fundamen-tal understanding of tumor initiation, progression, and metastasis. Until recently, genetically engineered mouse models (GEMMS) of cancer had lacked the genetic diversity found in human tumors, in which evolution may be driven by long-term carcinogen exposure and DNA damage. However, advances in sequencing technology and in our understanding of the drivers of genetic instability have given us the knowledge to generate new mouse models, offering an approach to functionally explore mechanisms of tumor evolution.

Automated summary

Cancer undergoes clonal evolution with high intratumor heterogeneity, influenced by both internal and external factors. Advances in sequencing technology have enabled the creation of diverse mouse models to explore mechanisms of tumor evolution.