Mouse models of muscle-invasive bladder cancer: Key considerations for clinical translation based on molecular subtypes

Context

In the past few years, research has suggested that molecular subtypes in muscle-invasive bladder cancer (MIBC) may be exploited to accelerate developments in clinical disease management and novel therapeutics.

Objective

This review summarises the existing MIBC mouse models from a molecular subtype perspective, their advantages and limitations, and their applications in translational medicine, based on a Pubmed search for publications from January 2000 to February 2018.

Evidence Acquistion

Publications relevant to MIBC mouse models and their molecular subtypes were identified in a literature review.

Evidence Synthesis

We classified the models based on the technique used for their establishment. For xenotransplant and allograft models, the inoculated cells and inoculated locations are the major determinants of molecular subtypes. Although the cell lines used in the xenotransplant models can cover most of the basal-squamous and luminal subtypes, allograft models offer a more realistic environment in which to reconstruct aspects of the associated stromal and immune features. Autochthonous models, using genetic and/or chemical stimuli to induce disease progression, can also generate models with basal-squamous and luminal subtypes, but further molecular characterisation is needed since other mutational variants may be introduced in these models.

Conclusions

We have identified preclinical models with different subtype specifications and assessed their promise and current limitations. These models are versatile tools which can reproduce the molecular complexity of the disease and support novel therapeutic development.