Abstract 2553: Functional precision medicine as a valid tool in glioblastoma clinical practice
Authors: Nam-Gu Her, Adelheid Woehrer, Gi Ju Lee, Seung Yoon Hyun, Jae Woo Ahn, Ji Soo Kang, Ryu I Hwang, Amin El-Heliebi, Barbara Prietl, Stefanie Stanzer, Thomas R. Pieber, Do-Hyun Nam
Journal: Cancer Research (2024)

Abstract Background: Glioblastoma remains a formidable therapeutic challenge, necessitating innovative strategies such as functional precision medicine (FPM). FPM offers personalized treatment by utilizing high-throughput screening of 10-100 compounds on patient-derived tumor cells (PDCs), assessing both efficacy and relative sensitivity, with results reported to the molecular tumor board within 2 weeks. The focus of this study is the cross-laboratory validity of this approach in glioblastoma, an essential step towards confirming FPM's consistency and potential as a game-changing tool in personalized cancer treatment. Methods: Patient-derived tumor cells from glioblastoma cases were cultured for 3-7 days followed by automated high-throughput screening. The drug library contained ~80 compounds, including specific numbers of cytotoxic and targeted drugs. Drug response curves informed the calculation of sensitivity scores, which were compared to the AimedBio reference library to identify potentially effective drug candidates for a given patient. Additionally, corresponding tumor tissues were analyzed through panel sequencing of 50 glioma-related genes. Results: A total of &amp;gt;50 patients with glioblastoma were included, with subgroups from CBmed, Austria, and AimedBio, South Korea. PDC cultures were successful in over 90% of cases, and informative high-throughput drug screening results were obtained. Integration of drug response with genetic tumor profiles yielded testable treatment candidates. Additionally, transcontinental shipping and re-screening of PDCs yielded comparable results, affirming the robustness of the method. Conclusion: This study establishes and validates high-throughput drug screening platforms specifically tailored for functional precision medicine, utilizing glioblastoma as a model. The findings reveal a high degree of validity in the drug screening results, reinforced by the excellent performance of both technical and biological replicates. Such success not only lays a solid foundation for further academic and pharmaceutical collaborations but also opens the path for regulatory approval, bringing the platforms one step closer to clinical implementation. Funding: K1 COMET Competence Centre CBmed, funded by the Federal Ministry of Transport, Innovation and Technology; the Federal Ministry of Science, Research and Economy, Land Steiermark (Dep. 12, Business and Innovation), the Styrian Business Promotion Agency (SFG), and the Vienna Business Agency. COMET is executed by the Austrian Research Promotion Agency (FFG). Citation Format: Nam-Gu Her, Adelheid Woehrer, Gi Ju Lee, Seung Yoon Hyun, Jae Woo Ahn, Ji Soo Kang, Ryu I Hwang, Amin El-Heliebi, Barbara Prietl, Stefanie Stanzer, Thomas R. Pieber, Do-Hyun Nam. Functional precision medicine as a valid tool in glioblastoma clinical practice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2553.