Abstract 4705: FreezeO organoid biobank: A translational pipeline for precision oncology at the University Medical Center Freiburg

Abstract The FreezeO Organoid Biobank at the University Medical Center Freiburg represents an innovative resource and an integral extension of the Molecular Tumor Board (MTB) that enables patient-specific drug testing for precision oncology. The focus of this biobank is to isolate and culture patient-derived organoids (PDOs) from fresh tumor biopsies, particularly from metastatic sites, to address an unmet need for therapy recommendations in advanced cancer. Our workflow begins when the MTB decides to obtain new tumor biopsies for whole exome sequencing (WES) or RNA sequencing (RNA-Seq). Whenever possible, PDO cultures are established in parallel to generate living tumor models. Once molecular profiling is complete, the targeted therapies recommended by the MTB are tested on the PDOs using an established semi-automated drug testing platform. Response to therapy is assessed and validated using complementary methods such as Western Blotting and transcriptomic analysis of the treated PDOs. The results will be rapidly integrated into MTB discussions and provide important data to refine and personalize treatment decisions. To date, we have successfully established and biobanked PDOs from nine different cancer types, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and rare cancers such as jejunum carcinoma. Remarkably, 60% of our biobank consists of PDOs derived from metastatic lesions, highlighting a clear benefit for late-stage cancer patients in the future. Drug tests were carried out on the PDOs within a clinically relevant timeframe and the results were included in the MTB decision-making process. Among the cases we will present, we report a metastatic CRC case featuring a PDO from a lung metastasis harboring a KRAS G12V mutation. Based on the oncologist’s recommendation, the drug testing strategy focused on the combination of Lapatinib and Trametinib. This approach reflects the ongoing clinical interest in overcoming intrinsic and acquired resistance to EGFR-targeted treatments in CRC. The inhibitor combination demonstrated promising efficacy in the PDO model. The robustness of these findings was validated through Western Blot analysis and RNA sequencing, providing critical data to inform the MTB panel. Ultimately, this evidence was instrumental in tailoring a more informed treatment strategy. The FreezeO Organoid Biobank demonstrates the translational potential of PDOs in precision oncology, particularly in metastatic disease. By seamlessly integrating rapid organoid culture, molecular profiling and targeted drug testing, our pipeline supports the MTB in making the most informed, data-driven treatment recommendations. This approach not only reinforces therapeutic decision making, but also underscores the utility of PDOs as a bridge between research and clinical application, paving the way for broader adoption in personalized oncology. Citation Format: Rhena F. Klar, Georg Vladimirov, Tanja Werner, Tamara Sloboda, Patrick Metzger, Maria E. Hess, Andreas Blaumeiser, Jasmin Traichel, Linus Schömig, Lioba Klaas, Maryam Barsch, Heiko Becker, Christopher Berlin, MTB Freiburg Network, Alexandra Nieters, Michael Quante, Tilman Brummer, Melanie Boerries. FreezeO organoid biobank: A translational pipeline for precision oncology at the University Medical Center Freiburg [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 4705.