Abstract
The goal of this review is to pinpoint the specific features, including the weaknesses, of various tumor models, and to discuss the reasons why treatments that are efficient in murine tumor models often do not work in clinics. In a detailed comparison of transplanted and spontaneous tumor models, we focus on structure–function relationships in the tumor microenvironment. For instance, the architecture of the vascular tree, which depends on whether tumor cells have gone through epithelial-mesenchymal transition, is determinant for the extension of the spontaneous necrosis, and for the intratumoral localization of the immune infiltrate. Another key point is the model-dependent abundance of TGFβ in the tumor, which controls the variable susceptibility of different tumor models to treatments. Grounded in a historical perspective, this review provides a rationale for checking factors that will be key for the transition between preclinical murine models and clinical applications.
Highlights
Murine tumor models have proven to be useful for our understanding of biological processes that take place during tumor growth, and for the preclinical development of antitumor therapies
We will take advantage of two models, in which TP and SP tumors can be obtained with isogenic tumor cells
For the functional analysis in TP and SP tumors, we examine a series of key tumor features: vascularization, growth rate, immune infiltrate and inflammation, tumor metabolism, and influence of tumor-derived TGFb
Summary
Murine tumor models have proven to be useful for our understanding of biological processes that take place during tumor growth, and for the preclinical development of antitumor therapies. Numerous antitumor drugs that were shown to be efficient in mice ended up being unusable against human tumors. Even if such a major failure has already been discussed, this problem still needs to be examined in depth. We will take advantage of two models (a mammary tumor and a melanoma), in which TP and SP tumors can be obtained with isogenic tumor cells. This comparison will be made for the first time by taking into account global structural and functional points of view.
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