miRNAs and androgen deprivation therapy for prostate cancer

Abstract

Androgen deprivation therapy (ADT) is mainly used for the treatment of advanced, metastatic or recurrent prostate cancer (PCa). However, patients progress to ADT resistance and castration-resistant prostate cancer (CRPC) with a poor prognosis. Reliable validated markers of ADT resistance with proven clinical utility are necessary for timely correction of the therapy as well as for improvement of patient quality of life. MiRNAs involved in the ADT response and CRPC development via multiple mechanisms may act as biomarkers for patient outcomes. Available data on miRNAs associated with the ADT response (resistance and sensitivity) are summarized and analyzed in the manuscript, including analyses using bioinformatics resources. Molecular targets of miRNAs, as well as reciprocal relations between miRNAs and their targets, were studied using different databases. Special attention was dedicated to the mechanisms of ADT resistance and CRPC development, including testosterone, PI3K-AKT, VEGF pathways and associated genes. Several different approaches can be used to search for miRNAs associated with the ADT response, each of which focuses on the associated set of miRNAs - potential markers of ADT. The intersection of these approaches and combined analysis allowed us to select the most promising miRNA markers of the ADT response. Meta-analysis of the current data indicated that the selected 5 miRNAs (miRNAs - 125b, miR-21, miR-23b, miR-27b and miR-221) and 14 genes are involved in the regulation of key processes of CRPC development and represent the most promising predictors of the ADT response, further demonstrating their potential in combination therapy for advanced PCa.

Keywords: ADT; Androgen deprivation therapy; Castration-resistant prostate cancer; Prostate cancer; Therapy effectiveness; miRNA markers.