Abstract 29: The utilization of patient-derived organoids as a platform for drug screening: Chemotherapy, targeted therapy, and immunotherapy

Abstract Cancer is one of a leading cause of mortality worldwide, with current treatments facing limitations such as drug resistance and relapse. To address these issues, the use of advanced in vitro models, such as patient-derived organoids (PDOs), is crucial. Unlike conventional 2D cultures, PDOs closely resemble the biological characteristics of tumors, thereby allowing the prediction of responses to drugs and supporting personalized therapies. Gradiant Bioconvergence (GBCC) has established a biobank comprising over 800 PDOs derived from tissue or metastatic samples of patients with lung, colorectal, gastric, pancreatic, and ovarian cancers. The biobank also includes NGS datasets of genomics and transcriptomics, as well as clinical information, including treatment history, and autologous peripheral blood mononuclear cells (PBMCs) or tumor infiltrating lymphocytes (TILs). PDOs are highly effective models for evaluating drug efficacy in vitro, capable of predicting clinical drug responses and providing valuable insights for the development of new therapeutics. GBCC has developed two distinct organoid-based drug screening platforms for evaluating various cancer therapies. The first drug screening platform employs organoids alone to evaluate anti-cancer drugs, including chemotherapy and targeted therapy. Additionally, the platform is capable of supporting mono or combination drug screenings. Of note, lung PDOs with driver mutations, such as EGFR and KRAS, demonstrated responsiveness to targeted drugs, with results that aligned with the patient’s treatment history. Antibody-drug conjugates (ADCs), including Trastuzumab Deruxtecan (T-DXd), exhibited sensitivity in HER2-overexpressing gastric cancer organoids and lung cancer organoids with HER2 mutations. To evaluate immune checkpoint inhibitors (ICIs), the GBCC has developed a second drug screening platform using autologous T cell co-culture with organoid models. Flow cytometry was employed to ascertain organoid viability and cytokine release by T cells, thereby confirming that the viability of cancer organoids was reduced in the presence of ICIs. The results demonstrate that our organoid-based drug screening platforms can be utilized to assess drug responsiveness, thus representing a valuable tool for the preclinical evaluation of drugs, and supporting the advancement of precision medicine and the discovery of new anti-cancer drugs. Citation Format: Na-Gyeong Lee, Misun Park, Sang-Eun Park, Hyeon-A Kim, Sang-yeon Lee, Jinguen Rheey, Ji-Yeon Park. The utilization of patient-derived organoids as a platform for drug screening: Chemotherapy, targeted therapy, and immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 29.