Androgen Deprivation Therapy Potentiates the Efficacy of Vascular Targeted Photodynamic Therapy of Prostate Cancer Xenografts

Purpose: WST11 vascular targeted photodynan therapy (VTP) is a local ohlation approach relying upon rapid, free radical-mediated desiniction of tumor vasculature. A phase III trial showed that VIP significantly reduced disease progression when compared with active surveillance in patients with low-risk prostate cancer. The aim of this study was to identify a (huggable pathway that could be combined with VIP to improve its efficacy and applicability to higher risk prostate cancer tumors. Experimental Design: Transcriptome analysis of VIP-treated tumors (IN-CaP-AR xenografts) was used to identify a candidate pathway for combination therapy. The efficacy of the combination therapy was assessed in mice bearing INCaP-AR or VCaP tumors. Results: Gene set enrichment analysis identifies the enrichment of androgen-responsive gene sets within hours after VTP treatment, suggesting that the androgen receptor (AR) may be a viable target in combination with VIP. We tested this hypothesis in mice bearing LNCaP-AR xenograft tumors by using androgen deprivation therapy (ADT), degarelix, in combination with VIP. Compared with either AD'F or VII' alone, a single dose of degarelix in concert with VIP significantly inhibited tumor growth. A sharp decline in serum prostate-specific antigen (PSA) confirmed AR inhibition in this group. Tumors treated by VIP and degarelix displayed intense terminal deoxynucleotidyl transferase-mediated DUTP nick end labeling staining 7 days after treatment, supporting an increased apoptotic frequency underlying the effect on tumor inhibition. Conclusions: Improvement of local tumor control following androgen deprivation combined with VIP provides the rationale and preliminary protocol parameters for clinical trials in patients presented with locally advanced prostate cancer. (C) 2018 AACR.