Wnt Signaling and Therapeutic Resistance in Castration-Resistant Prostate Cancer.

Curr Pharmacol Rep

Department of Urology, University of California, Irvine, 101 The City Drive South, Rt.81 Bldg.55 Rm.204, Orange, CA 92868, USA.

Published: October 2023

Purpose Of Review: Castration-resistant prostate cancer (CRPC) is a lethal form of prostate cancer (PCa) due to the development of resistance to androgen deprivation therapy and anti-androgens. Here, we review the emerging role of Wnt signaling in therapeutic resistance of CRPC.

Recent Findings: Convincing evidence have accumulated that Wnt signaling is aberrantly activated through genomic alterations and autocrine and paracrine augmentations. Wnt signaling plays a critical role in a subset of CRPC and in resistance to anti-androgen therapies. Wnt signaling navigates CRPC through PCa heterogeneity, neuroendocrine differentiation, DNA repair, PCa stem cell maintenance, epithelial-mesenchymal-transition and metastasis, and immune evasion.

Summary: Components of Wnt signaling can be harnessed for inhibiting PCa growth and metastasis and for developing novel therapeutic strategies to manage metastatic CRPC. There are many Wnt pathway-based potential drugs in different stages of pre-clinical development and clinical trials but so far, no Wnt signaling-specific drug has been approved by FDA for clinical use in CRPC.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664806PMC
http://dx.doi.org/10.1007/s40495-023-00333-zDOI Listing

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