PO-439 Establishment and characterisation of prostate cancer patient-derived organoids and cells

Abstract

IntroductionThe currently available cancer models fail to recapitulate the heterogeneity of Prostate cancer (PCa), its metastasis, and progression to castration-resistant states. 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 render 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 two-dimensional (2D) cell lines, then characterise these models to identify potential prognostic biomarkers and treatments for PCa while correlating the outcome with the collected clinical parameters.Material and methodsWe are employing the R-spondin-1 based organoids technology to generate PCa organoids and primary cell lines derived from fresh unaffected and tumour tissues of treatment-naïve patients undergoing radical prostatectomy. Consequently, molecular characterisation of the different patient-derived PCa organoids and cell lines will be performed, followed by assessing different classical and in-clinical trial drugs.Results and discussionsWe were successful in generating 26 unaffected and 24 tumour patient-derived organoids, out of a total of 30 patients, and capable of culturing 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 30 passages (more than 3 months). Our preliminary data indicates that our patient-derived organoids and cell lines show a typical epithelial phenotype and express Cytokeratin 5, Cytokeratin 8, Androgen Receptor and Prostate Specific Antigen. These models were further used to assess clinically used drugs and treatment approaches including chemotherapeutic agents (Docetaxel), Androgen-deprivation therapy (Bicalutamide and Enzalutamide). Our results show differential drug effects from one patient to the other.ConclusionIn this study, we are employing a novel methodology to establish patient-derived 3D organoids and cells to be used as a model for drug screening and to further characterise the mutational landscape of PCa. Consequently, the molecular characterisation of this model when combined with pharmacological profiles can aid in personalising the treatment of PCa.