Table 4 Advantages and disadvantages of using 3d organoids as preclinical models

Recreation of Complex Tumor Microenvironments: 3D organoids recreate complex tumor microenvironments, offering a physiologically relevant model for assessing the effects of PI3K inhibitors in a controlled laboratory setting

Incomplete Replication of Tumor Microenvironment Complexity: 3D organoids may not fully replicate the complexity of the tumor microenvironment compared to in vivo models, limiting the assessment of immune responses and drug penetration

Physiologically Relevant Model: 3D organoids preserve genetic and molecular characteristics of patient tumors, including altered PI3K signaling, providing a personalized approach to drug screening and enabling assessment of individual patient responses to PI3K inhibitors

Lack of Immune Cells and Limited Vasculature: The absence of immune cells and limited vasculature in organoids may restrict the evaluation of immune responses and drug penetration. Ongoing efforts to integrate immune cells and vasculature aim to address these limitations

Structural and Functional Similarities to Original Tumor: 3D organoids exhibit structural and functional similarities to the original tumor, allowing the study of important aspects like invasion and metastasis. This provides insights into the effects of PI3K inhibitors on tumor behavior

High-Throughput Drug Screening: High-throughput drug screening with 3D organoids enables testing of a broad range of PI3K inhibitors and combination therapies simultaneously, offering valuable insights into drug efficacy and identifying candidates for further development

Long-Term Culture and Monitoring: 3D organoids allow for long-term culture and monitoring of therapeutic response, facilitating the assessment of both short-term and long-term effects of PI3K inhibitors and identification of potential resistance mechanisms