Tumor-Derived Organoid Culture for Functional Personalized Oncology in Cholangiocarcinoma

Presenter: Ali Zarrinpar MD, PhD | University of Florida Background: Given the low incidence of tumors such as cholangiocarcinoma (CCA), it is difficult to establish the efficacy of standard treatment protocols with any certainty. This compels clinicians to select therapeutic approaches based on anecdotal evidence or small case series. The advent of tumor genetic sequencing has not resulted in substantial changes in treatment choices, as these fail to identify targets in the vast majority of cases. We have developed a high-throughput functional assay to test a library of targeted drugs against individual patient-derived tumor organoids from CCA. We seek to show the feasibility of this approach to yield experimentally-validated therapeutic options for patients. Methods: Four consecutive patients with CCA who were undergoing a planned standard of care biopsy or resection were enrolled in an IRB-approved prospective pilot study. Approximately 200 mg of tumor was shipped on ice overnight to SEngine Precision Medicine for growth of tumor-derived organoid culture and analysis of drug sensitivities. Organoids were evaluated using a multi-dose response to each drug in a library of 120 FDA-approved and investigational drugs. These Results were compared to all previous patients. This established both functional sensitivity and the uniqueness of each patient’s response. Results: Patient characteristics such as demographics, tumor pathology, Next Generation Sequencing (NGS) recommendations, and organoid-derived drug recommendations are shown in the Table. We optimized operational logistics, assessed tumor growth rates, and measured chemosensitivity reporting timelines. All four specimens resulted in adequate growth to characterize drug sensitivities. No NGS studies performed on these tumors resulted in targeted chemotherapy recommendations. Conversely, tumor organoid assays rapidly identified selective, personalized drugs in all four cases. Conclusion: We have shown the feasibility of this approach in CCA. This pilot study has facilitated the expansion process, quantified the turn-around time, and identified technical and logistic barriers for future clinical trials. Our preliminary Results will inform the design of a future prospective clinical trial to establish and validate this method to select personalized cancer treatments for rare malignancies.