Preclinical Trials in Mouse Cancer Models

Abstract

The goals of this chapter are to address general principles involved in testing cancer therapeutics in the mouse with an emphasis on how murine cancer models might be deployed to overcome some of the difficulties involved in evaluating new agents in human beings. We compare xenograft systems with genetically engineered models and discuss the benefits and drawbacks of each. We suggest criteria that should be considered in designing and implementing preclinical trials in mouse models.

Mouse Models of Brain Tumors and Their Applications in Preclinical Trials

“…In principle, strains of mice forming spontaneous tumors due to mutations in the genes characteristic of a human malignancy are appealing due to predictability of the tumor-initiating lesion(s), immunocompetence, and tumor development at the appropriate site. Such spontaneous tumor formation recapitulates complex processes of ever-changing tumor genetic makeup, angiogenesis, tumorhost interactions, metastasis to distant sites, and can provide invaluable insights onto efficacy of single or multiple drug treatment on the preformed tumor (14). In addition, use of faithful GEMs is essential for modeling less common cancers due to limited patient population.…”

“…More complications arise from the fact that mutant alleles are often expressed or deleted from the whole animal or tissue, compared with human tumors that are thought to arise from a single mutant cell or a small mutant cell population. In this aspect, GEMs are more representative of human cancer predisposition syndromes rather than random tumorigenesis: presence of tumor-initiating mutation(s) in a large cell population may result in tumors characterized by decreased cell heterogeneity (14). In addition, promoters used for gene targeting might affect cell population different from the one that normally gives rise to corresponding human tumors.…”