Mouse models of human bladder cancer as a tool for drug discovery

Area of Science:

• Oncology
• Preclinical Research
• Mouse Models

Background:

• Muscle-invasive bladder cancer (MIBC) is a life-threatening malignancy with limited therapeutic options.
• Effective preclinical models are crucial for advancing MIBC treatment strategies.
• Current research highlights the need for robust animal models to test novel therapeutic agents.

Purpose of the Study:

• To describe and validate mouse models for preclinical evaluation of therapies targeting muscle-invasive bladder cancer.
• To provide detailed protocols for utilizing these models in drug discovery pipelines.
• To demonstrate the application of these models using mTOR inhibitors as an example.

Main Methods:

• Generation of a genetically engineered mouse model (GEMM) of bladder cancer via adenovirus-Cre delivery.
• Establishment of an orthotopic mouse model by intravesical instillation of human bladder tumor cells into immunocompromised mice.
• Detailed protocols for preclinical assessment of new chemical entities within these models.

Main Results:

• Successfully established and characterized both GEMM and orthotopic mouse models for bladder cancer.
• Demonstrated the utility of these models in evaluating the efficacy of therapeutic agents, exemplified by mTOR inhibitors.
• Provided reproducible protocols for preclinical drug testing in bladder cancer research.

Conclusions:

• The described mouse models offer valuable platforms for the preclinical evaluation of novel therapies for muscle-invasive bladder cancer.
• These models facilitate the assessment of drug efficacy and mechanism of action in a relevant biological context.
• The established protocols support the advancement of drug development for MIBC, addressing an unmet clinical need.