Abstract 1993: A translational circulating tumor cell drug sensitivity screening platform for integrated drug development and precision medicine: Results from Antrodia cinnamomea profiling

Abstract Reliable preclinical drug sensitivity screening platforms are crucial for advancing precision medicine and drug development. We have established a circulating tumor cell (CTC) drug sensitivity screening platform that enables comprehensive applications, including treatment response prediction and molecular profiling. To demonstrate the platform's utility, we evaluated multiple compounds including Antrodia cinnamomea (AC) and standard chemotherapy across various cancer types. For the AC study, CTCs were isolated from patients (n=9) with brain tumors (n=3), osteosarcoma (n=2), renal cell carcinoma (n=1), small cell lung cancer (n=1), breast cancer (n=1), and colon adenocarcinoma (n=1). CTCs were expanded using the E.V.A. Select platform with biomimetic 3D surface structure. Cells were treated with AC (0-125 μg/mL) and responses were compared with platinum-based chemotherapy (cisplatin/carboplatin). Cell viability was assessed using CellTiter-Glo® luminescent assay after 72 hours. Our platform has also demonstrated capability for next-generation sequencing in separate drug discovery cohorts. Data analysis was assisted by artificial intelligence tools (Claude, Anthropic). AC demonstrated consistent dose-dependent cytotoxicity, with survival rates at 125 μg/mL ranging from 5.7-13.8% across cancer types. Compared to platinum drugs (survival rates 22-67%), AC showed stronger or comparable efficacy. Brain tumor samples showed particular sensitivity to AC (125 μg/mL: 5.7-13.8% survival vs. cisplatin: 66.5% survival). Osteosarcoma samples demonstrated consistent AC response (125 μg/mL: 6.1-10.0% survival vs. carboplatin: 31.4-43.5% survival). The platform has successfully supported both drug sensitivity screening and molecular profiling across multiple drug development programs. This study showcases our platform's versatility in drug sensitivity screening and comprehensive drug development applications. The E.V.A. Select platform supports both drug response profiling and molecular characterization, making it a valuable tool for drug discovery and precision medicine applications. These capabilities enable systematic evaluation of novel compounds while supporting mechanistic understanding through molecular analyses. Citation Format: Chia-Liang Yen, Pei Yu Chen, Shih Pei Wu. A translational circulating tumor cell drug sensitivity screening platform for integrated drug development and precision medicine: Results from Antrodia cinnamomea profiling [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 1993.