Abstract 1699: A study on prediction model of drug sensitivity using patient-derived organoids

Abstract Background: Cancer treatment is increasingly based on precision medicine, which tailors therapies to the genetic and biological characteristics of a patient's tumor. PDOs offer a promising platform for predicting drug sensitivity, helping to identify effective therapies. However, existing models still face limitations in replicating clinical tumor heterogeneity and predicting drug responses accurately. In this study, we developed a novel two-dimensional (2D) culture system (2DO) for CRC PDOs that improves reproducibility and better mirrors the tumor microenvironment compared to traditional methods. Purpose: The goal of this study is to evaluate the effectiveness of PDO-based drug sensitivity assays in predicting clinical outcomes for CRC patients. We aim to explore the potential of PDO assays in personalized treatment strategies, improving CRC treatment outcomes. Methods: Tumor samples from CRC patients were obtained via surgery or endoscopic biopsy. These tumors were washed, dissociated, and filtered to isolate viable tumor cells, which were then cultured as PDOs under optimized conditions that preserve the tumor’s genetic and phenotypic characteristics. Drug sensitivity assays were performed by treating PDOs with different chemotherapeutic agents and measuring cell proliferation using a method: the Incucyte system (SARTRIUS, Germany) for live-cell imaging. Results: Drug sensitivity assays using PDOs showed promising results. The Incucyte system had a positive predictive value (PPV) of 75% and a negative predictive value (NPV) of 33% when compared to clinical outcomes. This result suggests that PDOs are useful for predicting tumor response to chemotherapy, though improving the NPV is necessary for more reliable predictions. The combination of imaging and biochemical assays offered a comprehensive evaluation of drug effects, and the PDOs closely mimicked patient-specific treatment responses. Conclusion: This study demonstrates the potential of PDO-based drug sensitivity assays as a tool for personalized treatment in colorectal cancer. While promising, further refinement is needed, particularly in improving the negative predictive value, to optimize PDO models for clinical use. PDO-based assays may help bridge the gap between laboratory findings and real-world therapeutic outcomes, contributing to more individualized cancer treatments in the future. Citation Format: Rie Hayashi, Norikatsu Miyoshi, Rie Mizumoto, Kengo Haruna, Shiki Fujino, Mitsunobu Takeda, Yuki Sekido, Tsuyoshi Hata, Atsushi Hamabe, Takayuki Ogino, Mamoru Uemura, Yuichiro Doki, Hidetoshi Eguchi. A study on prediction model of drug sensitivity using 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 1699.