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Table 3 Advantages and disadvantages of using genetically engineered mouse models as preclinical models

From: Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway

Advantages of genetically engineered mouse models as pre-clinical models

Disadvantages of genetically engineered mouse models as pre-clinical models

Mimicking Molecular Properties of Human BC: GEMM enables the introduction of specific genetic alterations, closely mimicking the molecular properties of human breast cancer, including the activation of the PI3K pathway

Time-Consuming and Expensive: Creating and maintaining GEMM can be time-consuming and expensive, limiting the scalability and efficiency of experiments

Representation of BC Development and Progression: GEMM captures breast cancer's complex development and progression, modeling the stepwise transition from preinvasive lesions to invasive tumors. It provides insights into early tumorigenesis and the effects of PI3K inhibitors at various stages

Limited Reflection of Mutational Landscape: GEMM's introduced genetic alterations may not fully reflect the mutational landscape of human breast cancer, raising concerns about the representativeness of these models

Comprehensive Assessment of Tumor Dynamics: GEMM enables a comprehensive assessment of tumor dynamics, including growth, metastasis, and interactions with the microenvironment, offering a holistic view of breast cancer biology

Integration with Other Models and Clinical Data: To comprehend the effects of PI3K inhibitors in breast cancer, insights from GEMM should be integrated with other preclinical models and clinical data to address potential limitations in genetic fidelity and capture the heterogeneity observed in human tumors

Therapeutic Efficacy and Toxicity Assessment: GEMM allows for the evaluation of therapeutic efficacy and toxicity of PI3K inhibitors by monitoring tumor response, assessing histopathological changes, and analyzing molecular alterations in tumor tissue

 

Mechanistic Studies for Drug Response and Resistance: GEMM enables mechanistic studies to understand the molecular mechanisms of response and resistance to PI3K inhibitors. Gene expression manipulation within specific cell types or tumor subtypes helps uncover the role of individual genes or pathways in drug sensitivity or resistance

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