Abstract A006: Development of a circulating tumor cell-derived cancer organoid platform for drug screening against metastatic tumors and longitudinal monitoring of drug resistance
Authors: Yi-chun Han, David Hsieh, Ruobo Zhang, Emily Miyashita-Lin, Shian-Jiun Shih
Journal: Clinical Cancer Research (2024)

Abstract Metastatic disease remains the primary cause of cancer-related deaths, presenting a significant challenge in oncology drug development. Current drug screening efforts often rely on cell lines or primary tumor-derived models, which may not adequately mimic the behavior of metastatic tumors. To address this, we aimed to develop a system that more accurately reflects metastatic tumors for improved drug screening. We leveraged a specialized culture platform featuring patented coated plates and proprietary media developed by AcroCyte (Taiwan) to cultivate circulating tumor cells (CTCs) into cancer organoids without pre-selection or enrichment. Building on our previous work, where we successfully cultivated CTCs from fresh blood and cryopreserved peripheral blood mononuclear cells (PBMCs) from renal, colon, and lung cancer patients into cancer organoids, we have now demonstrated the ability to freeze these CTC- derived organoids and thaw them for new culture when needed. We also present new data extending this success to breast and prostate cancers. CTCs from five frozen PBMC samples from breast cancer patients and three from prostate cancer patients formed visible colonies, with positive immunostaining for EpCAM, cytokeratin, and CD44. The immune cells in the PBMC samples gradually died off within three weeks of culture, as confirmed by the absence of CD45- positive cells. Interestingly, CTC-derived organoids from breast and prostate cancers did not form the spheroids observed in renal, colon, and lung cancer models. Instead, they appeared as colonies or clusters of CTCs. After 6-8 weeks of active growth, these clusters exhibited a slower growth rate, although they remained viable in the proprietary culture system. We are actively evaluating various culture media supplements, tailored to breast and prostate cancers, to extend the active growth period of these CTC-derived organoids for longer durations. Importantly, these CTC-derived colonies retained drug sensitivity, demonstrating the system's potential for effective drug screening against metastatic tumors. Our platform now supports organoid development from renal, colon, lung, breast, and prostate cancers, and we are actively expanding to include all major solid tumors. Since this technology uses blood, which can be obtained non-invasively, it enables longitudinal monitoring of CTCs as a functional liquid biopsy. Additionally, frozen PBMCs can be used as a source material for CTCs, and the resulting organoids can be utilized for drug sensitivity testing. This platform could be instrumental in oncology drug development and holds promise for monitoring emerging drug resistance in clinical trials by analyzing PBMC samples collected before and after treatment, offering a functional liquid biopsy-based approach to aid in developing therapies targeting metastatic disease. Citation Format: Yi-chun Han, David Hsieh, Ruobo Zhang, Emily Miyashita-Lin, Shian-Jiun Shih. Development of a circulating tumor cell-derived cancer organoid platform for drug screening against metastatic tumors and longitudinal monitoring of drug resistance [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A006.