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Organoids are a widely used 3D culture system that has the potential to recapitulate the profile and phenotype of physiological cells. The culture of circulating tumor cells (CTCs) in this 3D system not only mimics the tumor physiological environment but allows researchers to test therapeutic responses to certain drugs based on a patient's own cancer phenotype. The purpose of our study is to perform an in vitro evaluation of patient-derived CTC organoids to more precisely identify personalized therapeutic options based on the response of these CTCs to each specified inhibitor. Using Astrin Bioscience’s proprietary CTC enrichment method, collected CTCs are plated as organoid cultures. The performance of our proprietary enrichment method has been assessed using both spiked cancer cell lines (in whole blood) and patient CTCs. We have successfully grown organoids from four prostate cancer cell lines and patient CTCs across multiple cancer types including pancreatic and liver adenocarcinoma. RNA sequencing of liver CTC organoids expressed EPCAM, a marker of CTC epithelial cells and coincided with data from a prostate epithelial cell line, LNCaP. This serves as robust evidence that our patient derived organoids truly originated as CTCs. Functional assays using different chemotherapies and targeted therapies will be applied to our organoid culture system. Drugs are uniquely selected for each patient based on cancer type, cancer stage and previous failed therapies. Efficacy of therapy is evaluated using imaging and cell viability assays to determine sensitivity or resistivity to each therapy. Transcriptomic and proteomic analyses will also be performed on these samples to aid in the identification of other predictive biomarkers and future novel therapy testing. Thus, this platform creates a pre-clinical drug screening tool to create a personalized guide to potential therapies for each patient. Citation Format: Catalina Galeano-Garces, Kaylee J. Smith, Nicholas Heller, Mahdi Ahmadi, Jiarong Hong, Jayant Parthasarathy, Justin M. Drake. CTC-derived organoids from liver and pancreatic cancer patients for personalized therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 191. |
