Wnt signaling in castration-resistant prostate cancer: implications for therapy

Increasing evidence has indicated that Wnt signaling plays complex roles in castration resistant prostate cancer (CRPC). Although not all data were consistent, β-catenin nuclear localization and its co-localization with androgen receptor (AR) were more frequently observed in CRPC compared to hormone naïve prostate cancer. This direct interaction between AR and β-catenin seemed to elicit a specific expression of a set of target genes in low androgen conditions in CRPC. Paracrine Wnt signaling also was shown to aid resistance to chemotherapy and androgen deprivation therapy. Results from the next generation sequencing studies (i.e. RNA-seq and whole exosome sequcing) of CRPC specimens have identified the Wnt pathway as one of the top signaling pathways with significant genomic alterations in CRPC, whereas, Wnt pathway alterations were virtually absent in hormone naïve primary prostate cancer. Furthermore, Wnt signaling has been suggested to play an important role in cancer stem cell functions in prostate cancer recurrence and resistance to androgen deprivation therapy. Therefore, in this review we have summarized existing knowledge regarding potential roles of Wnt signaling in CRPC and underline Wnt signaling as a potential therapeutic target for CRPC. Further understanding of Wnt signaling in castration resistance may eventually contribute new insights into possible treatment options for this incurable disease.