Human tumor xenografts and mouse models of human tumors: re-discovering the models

Abstract

Background: Human tumor xenografts constitute the major efficacy and tumor biology models for cancer drug discovery. Gene expression and protein expression technologies have improved understanding of the malignant diseases represented by human tumor lines. Genetically engineered mouse (GEM) models of cancer are improving and allow assessment of immune system-mediated therapeutics. Objective: The current brief review discusses the status of human tumor xenografts, GEM models and normal tissue assays used in cancer drug discovery. Results: The Preclinical Pediatric Tumor Program consortium with 47 molecularly well-characterized pediatric tumor xenografts is leading the field. Individual laboratory studies show no correlation between culture and in vivo characteristics of some human tumor lines. The TRAMP and RIP1TAG2 GEM models have been used for efficacy studies. Recent GEM models often have two mutated genes leading to greater genetic instability. Host normal cells are important contributors in malignant disease. While convenient and frequent subcutaneous tumor implantation does not provide an optimal microenvironment for modeling clinical disease. Orthoptopic tumor implantation is gaining in use due to the availability of labeled tumor sub-lines and non-invasive imaging techniques. Conclusion: The science associated with human tumor xenografts and GEM cancer models is not static. The application of gene and protein expression technologies, the wider availability of non-invasive imaging and improved genetic engineering are allowing improved tumor modeling. However, as more is learned about current models, it is becoming clear that there is a shortage of models to cover the broad spectrum of human malignant disease.

Keywords::

• genetically-engineered mice
• human tumor xenografts
• labeled tumors
• metastasis models
• tumor models