Murine models have served as a mainstay for preclinical cancer research trials for many decades, and continue to provide important insight into factors that influence malignant transformation of a tumor, tumor rate of growth, metastatic disease, and other activities. Two of the most widely used models include the mouse xenograft model and the genetically engineered mouse model (GEMM). A sophisticated understanding of any means is the key to maximizing the benefits of a particular resource that cannot otherwise be obtained. Both unique model types have played their part, contributing to important cancer treatment developments.

Mouse xenograft models are comprised of either human primary tumor samples or human cell lines, which are transplanted using subcutaneous or orthotopic techniques. Primary tumor grafts demonstrate a tumor’s complex heterogeneity and are also more representative of the individual patient than are uniform single cell lines. Orthotopic xenografts are applied to the same organ or tissue type as the tumor source, mimicking its original microenvironment. Mouse xenograft models demonstrate human tumor response to treatment, since human tumor grafts are used while incorporating its original microenvironment in humanized mice.

Genetically engineered mouse models demonstrate the role of specific genes in tumor development. Certain genes that are strongly associated with tumor progression and development are deleted, over-expressed, or mutated. With GEMMs, the tumor’s microenvironment is mimicked by the use of immunocompetent mice rather than athymic or immunocompromized mice. Since the tumor tissues are not transplanted, tumors using the GEMMs take more time to develop. However, GEMMs provide unique opportunities to study and observe tumor development in its various stages.

Strict guidelines are mandated to help ensure clinically relevant tumor models for cancer studies. For example, after a treatment under study is discontinued, a rebound effect is considered highly undesirable. Therapies applied to murine models must also be clinically relevant in regard to dosage and other measures. Additionally, preparation and utilization of various models are subject to strict, time-sensitive regimens. Researchers are empowered by a rich history behind the xenograft and genetically engineered models which enable them to continue to break new ground.

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Categories: Oncology

Tags: cancer research trials, Mouse xenograft models, tumor models