Chapter 5 - Protocols in genetic mice models of pancreatic cancer

Abstract

The high attrition rates in cancer drug discovery indicate that there is a need to revamp the ways in which precursor preclinical research is being performed. The majority of preclinical studies are either done in cancer cell lines (in 2D or 3D culture) or subcutaneous xenograft. Recently, patient derived xenograft (PDX) and patient organoid derived (PDOx) mice tumor models have emerged. However, these preclinical models are not truly reflective of the tumor heterogeneity and microenvironment. PDX are usually grown subcutaneously and are infiltrated with mouse stroma. The orthotopic models are developed by injecting an organoid suspension at the organ site. Unfortunately, the organoid models do not recapitulate the tumor mass which is composed of so many different types of closely knit cells (fibroblast, stellate, tumor cells, immune cells among others). Genetically engineered models are more representative of human tumors and recapitulate the microenvironment to a significant extent. Given they are developed in immune-competent mice, therefore, they also are able to help in immune-related cancer biology and drug discovery studies (though mice immune system). Although cumbersome and costly, genetic mice models serve as better models for cancer development and drug discovery studies. In this chapter, an attempt has been made to provide an overview of the protocols in genetic mice breeding with a focus on pancreatic cancer genetically engineered models.