A precision medicine approach in the management of men with biochemical recurrence of prostate cancer using patient specific in vitro prostate cancer cell line models

Introduction & Objectives: Precision medicine aims to provide the right treatment for the right patient at the right time. Tissue is required to facilitate this approach, however prostate cancer is challenging to culture in vitro. Recent development of novel organoid in vitro culture technology potentially allows the use of patient derived specimens for precision medicine (1). We aim to apply this technology to develop patient specific cell line models for drug testing and next generation sequencing as part of a precision medicine approach in recurrent prostate cancer. Methods: Patient derived metastatic tissue samples were collected as part of a larger clinical trial. These were digested in Type II Collagenase (Gibco) for 2 hours and seeded directly onto Collagen Type I coated plates in novel media. Samples were cultured in vitro for a minimum of 2 weeks prior to validation. PSA ELISA (GenWay Biotech) of conditioned media along with RT-qPCR comparison of various gene products of interest between cultured patient samples and established prostate cancer cell lines was performed. In vitro samples were subsequently utilised for therapeutic screening. Results: A total of 6 histologically proven patient samples were available for culture. Four patient samples were successfully grown in vitro. One patient sample was available for downstream analysis. Tissue was successfully cultured for a minimum of 2 weeks prior to validation. PSA ELISA was positive. RT-qPCR confirmed expression of prostate specific genes PSA, AR, FKBP5 and TMPRSS. Drug screen revealed a marked response to Docetaxel, Cabazitaxel and lesser response to anti-androgen treatments. Next generation sequencing is ongoing. Conclusions: We have successfully cultured patient derived samples for precision medicine. Further therapeutic screening and next generation sequencing of derived cultures is ongoing in order to potentially inform therapeutic strategies. Organoid in vitro culture technology could provide a vital stepping stone towards precision medicine in the future, involving the rapid generation of patient specific in vitro models for therapeutic screening to guide individualized treatment