Poster Presentation 29th Lorne Cancer Conference 2017

Characterising and modelling prostate cancer response to treatment (#142)

Michael Clarkson 1 2 , Nadia Tolich 1 , Natalie Kurganovs 1 , Anthony Costello 1 2 , Christopher M Hovens 1 2 , Niall M Corcoran 1 2
  1. University of Melbourne, Parkville, VIC, Australia
  2. Prostate Cancer Research Centre at Epworth, Melbourne, Vic, Aust

Prostate tissue response to androgen deprivation therapy (ADT) is poorly understood. To address this issue, we examined patient tissue following a super castration regimen. Patients were treated with a combination of Abiraterone, Degarelix, Bicalutamide and Prednisolone for 24 weeks and then underwent radical prostatectomy. Histological analysis revealed that, in our cohort of 16 super-castration patients we saw one case of near complete tumor regression and three cases of substantial reduction in tumor volume. This surprising result suggests that some individuals are inherently very sensitive to ADT. We conducted gene expression analysis (RNA-seq) on treated and untreated patient samples and obtained a list of differentially expressed genes that are potentially correlated with ADT resistance/sensitivity. Amongst other things, targets of the known survival promoting factor, STAT3, were upregulated. From these results we hypothesise that ADT induces a switch from an androgen dependent, to a STAT3 dependent, survival mechanism in prostate cells. It also raises the possibility that clinical use of ADT could potentially be augmented with STAT3 inhibition. In order to test these ideas we have been examining whether it is possible to recapitulate the ADT response we observed in clinical samples in a number of model systems including patient tissue explants and established prostate cancer cell lines. To date, this has revealed that some features of the ADT response are reproduced in LNCaP cells.