Abstract 5199: Enhancing precision medicine in advanced lung, gastric and rectal cancer: Exploring the reliability of Patient-derived organoids

Abstract Introduction: A significant challenge in cancer treatment is the development of effective therapies, particularly for patients with recurrent and advanced-stage cancers. Major barriers to successful treatment include the identification of druggable targets and the exploration of novel drug modalities. Investigating strategies for effective combination regimen with standard therapies or immuno-oncology (IO) agents is crucial for optimizing treatment sequences. Traditional clinical trials are resource-intensive and time-consuming; in contrast, patient-derived organoids facilitate the efficient testing of tailored combination therapies specifically for recurrent and metastatic patients. Method: We employed organoid cultures derived from patients with advanced lung, gastric and rectal cancer to assess their responses to a range of anticancer drugs, including standard agents, IO therapies, and radiotherapy. Drug responses and radiosensitivity data were correlated with matched clinical data, and metrics such as predictive accuracy, sensitivity, and specificity were calculated. The organoids were validated as reliable models reflecting clinical cancer behaviors, ensuring their relevance for evaluating treatment responses. Results: We investigated drug and radiation responses, molecular marker expression, and dynamic caspase imaging of patient-derived organoids, validating these findings in conjunction with clinical data. Our analysis revealed a significant correlation between organoid based in vitro responses and clinical observations, suggesting potential pathways for personalized treatment strategies in advanced cancer settings. The distinct in vitro response patterns observed in organoids align with clinical experiences, underscoring the importance of optimizing treatment sequences and evaluating novel drug modalities alongside immunotherapy. Conclusion: This research highlights the efficacy of patient-derived organoids (PDOs) in evaluating treatment responses, thereby contributing to the advancement of precision oncology for patients with advanced lung, gastric and rectal cancer. The findings underscore the importance of using PDOs as reliable preclinical models to tailor therapeutic strategies based on individual patient profiles. Future studies should focus on leveraging organoid models to optimize combinations of targeted therapies, radiotherapy and immuno-oncology agents, ultimately aiming to enhance clinical outcomes and personalize treatment approaches for advanced stage cancers. Citation Format: Hye Ryeong Jun, Shin Young Chang, Hyoyoung Kim, Hyunki Kim, Minkyu Jung, Hye Ryun Kim, Tae Il Kim, Jung Eun Kim. Enhancing precision medicine in advanced lung, gastric and rectal cancer: Exploring the reliability of Patient-derived organoids [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 5199.