Preclinical murine tumor models: a structural and functional perspective

Area of Science:

• Oncology
• Translational Medicine
• Cancer Research

Background:

• Murine tumor models are crucial for preclinical cancer research.
• However, treatments effective in these models often fail in clinical settings.
• This discrepancy necessitates a deeper understanding of model limitations.

Purpose of the Study:

• To critically evaluate the strengths and weaknesses of various tumor models.
• To elucidate the reasons behind the poor translation of preclinical findings to clinical success.
• To identify key factors for improving the predictive value of preclinical models.

Main Methods:

• Comparative analysis of transplanted and spontaneous tumor models.
• Focus on structure-function relationships within the tumor microenvironment.
• Examination of factors like vascular architecture and immune cell infiltration.

Main Results:

• Tumor microenvironment features, such as vascularization and epithelial-mesenchymal transition, influence necrosis and immune cell localization.
• Transforming growth factor beta (TGFβ) abundance varies by model, affecting treatment susceptibility.
• Significant differences exist in how models mimic human tumor complexity.

Conclusions:

• Current murine tumor models possess limitations that hinder clinical translation.
• Addressing model-specific factors like tumor microenvironment and TGFβ is essential.
• A historical perspective guides the identification of critical parameters for successful preclinical-to-clinical transitions.