Abstract: PNFBA-08
Sources of Funding: ANZUP Tolmar Clinical Research Fellowship

Introduction

Precision medicine aims to provide the right treatment for the right patient at the right time with treatment directed on the basis of the targetable tumoral aberrations rather than just a traditional histologic subtype. However to facilitate this approach, clinicians require patient derived samples. Prostate cancer is challenging to culture in vitro. Recent development of novel organoid in vitro culture technology has led to the development of multiple new in vitro prostate cancer cell line models. We aim to apply organoid culture technology to develop novel in vitro prostate cancer cell line models and propagate patient derived samples to allow drug testing and next generation sequencing as part of a precision medicine approach to early 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 5 patient samples were available for culture with histologically proven metastatic prostate cancer. Tissue from a 67 year old male with biochemical recurrence of prostate cancer following retro-pubic radical prostatectomy was obtained fresh at time of salvage lymph node dissection (PSA was 1.5 ng/ml). Tissue was successfully cultured for a minimum of 4 weeks prior to validation. PSA ELISA of conditioned media 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 Enzalutamide and minimal effect to Bicalutamide.

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.

Funding

ANZUP Tolmar Clinical Research Fellowship