Abstract B090: Personalized research: Establishment and characterization of prostate cancer patient-derived organoids and cells

Abstract

Abstract Several attempts have been made to understand the exact mechanisms underlying the pathogenesis of prostate cancer (PC); however, the currently available cancer models fail to recapitulate the heterogeneity of this tumor, its metastasis, and progression to castration-resistant states. Moreover, many drug candidates that succeed in preclinical models fail to deliver a good outcome in clinical trials, resulting in ineffective patient treatment and misused resources. In this aspect, the development of three-dimensional (3D) organoid culture systems has rendered it feasible to recap the convolution of organogenesis in vitro, promoting the generation of novel and more representative cancer models. Thus, the aim of this study is to generate patient-specific 3D organoids and cell lines, then characterize these models to identify potential prognostic biomarkers and treatments for PC while correlating the outcome with the collected clinical parameters. In our study, we are employing the R-spondin-1-based organoids technology to generate PC organoids and primary cell lines derived from fresh normal and tumor tissues of patients undergoing radical prostatectomy. Consequently, molecular characterization of the different patient-derived PC organoids and cell lines will be performed, followed by using this model to assess different classical and in-clinical trials drugs. We succeeded in establishing 21 normal and 18 tumor patient-derived organoids, out of a total of 23 patients, and then propagated the established organoids for up to 6 generations. Interestingly, 2D cells were derived from these organoids using the same culture media and were continuously passaged for up to 20 passages so far (more than 3 months). Our newly patient-derived organoids and cells show a typical epithelial phenotype and express CK8 and CK14 (prostate epithelial markers). To the best of our knowledge, this is the first study to address the establishment of primary PC cell lines from organoids, which will likely lead to a comprehensive understanding of mechanisms exploited in PC. Moreover, molecular characterization of this model when combined with pharmacologic profiles can aid in predicting a patient’s drug response; thus, our study represents an attempt to inaugurate what can possibly lead to personalized treatment of PC. Citation Format: Katia Anis Cheaito, Ola Hadadeh, Hisham Bahmad, Marwan El-Sabban, Albert El-Hajj, Deborah Mukherji, Wassim Abou-Kheir. Personalized research: Establishment and characterization of prostate cancer patient-derived organoids and cells [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B090.