Androgen and Oestrogen Signalling Pathways in Prostate Hyperplastic Tissues: Opportunities for Therapeutic Targeting from Multiple Angles

Benign prostatic hyperplasia (BPH), a non-malignant neoplasm in ageing men, is the most frequent cause of urinary flow obstructions at the bladder neck. In addition to the clear evidence of testosterone-dihydrotestosterone dependency of BPH, involvement of the stroma, stromal–epithelial interactions and the role of oestrogens have gained much interest in the pathology of this disease. Pathology-based and target-based, two principal drug discovery, approaches have rendered us with 5α-reductase (5AR) inhibitors and aromatase (Aro) inhibitors in the management of BPH. But the clinical experience of long-term side effects and drug resistance with clinically approved finasteride, dutasteride and atmestane indicated that single targeting agents might not always produce the desired biological effect, even if the target is inactivated or inhibited. Multi-targeting therapeutics strategy has attracted considerable attention in the last decade for an additive or synergistic effect of a single drug acting on separate targets with improved therapeutic efficacy, safety and resistance. Using computational tools, we explored the multi-targeted therapeutic potential of reported 5-alpha reductase inhibitors in BPH management, after theoretical investigation against the aromatase enzyme. The screened compounds need to be experimentally validated using in vitro and in vivo models for their further clinical applications.