Table 5 Advantages and disadvantages of using co-culture models as preclinical models

Capture of Tumor Microenvironment Complexity: Co-culture models excel at capturing the complexity and heterogeneity of the tumor microenvironment by incorporating diverse cell types, including tumor and stromal cells, to replicate intricate interactions observed in vivo

Lack of Spatial Organization and 3D Structure: Co-culture models may lack the spatial organization and three-dimensional structure observed in patient tumors, potentially limiting their ability to fully replicate the in vivo environment

Physiologically Relevant Environment: Co-culture models, through the co-cultivation of tumor and stromal cells, offer a more physiologically relevant environment for evaluating the effects of PI3K inhibitors. This reflects the dynamic interactions crucial for tumor progression and response to therapy

Incomplete Replication of Tumor Microenvironment Complexity: While capturing complexity, co-culture models may not fully replicate the intricate and diverse aspects of the tumor microenvironment as observed in vivo

Study of Drug Resistance Mechanisms: Co-culture models facilitate the study of drug resistance mechanisms in the tumor microenvironment, enabling exploration of how stromal cells contribute to resistance. This aids in identifying molecular mechanisms and developing strategies to overcome resistance

Critical Selection of Stromal Cell Types and Ratios: The critical selection of stromal cell types and their ratios in co-culture systems is crucial for model relevance and accuracy. However, this selection process may pose challenges in fully reflecting the diversity of the in vivo tumor microenvironment