Abstract

Aberrant activation of the Wnt pathway is emerging as a frequent event during prostate cancer that can facilitate tumor formation, progression, and therapeutic resistance. Recent discoveries indicate that targeting the Wnt pathway to treat prostate cancer may be efficacious. However, the functional consequence of activating the Wnt pathway during the different stages of prostate cancer progression remains unclear. Preclinical work investigating the efficacy of targeting Wnt signaling for the treatment of prostate cancer, both in primary and metastatic lesions, and improving our molecular understanding of treatment responses is crucial to identifying effective treatment strategies and biomarkers that help guide treatment decisions and improve patient care. In this review, we outline the type of genetic alterations that lead to activated Wnt signaling in prostate cancer, highlight the range of laboratory models used to study the role of Wnt genetic drivers in prostate cancer, and discuss new mechanistic insights into how the Wnt cascade facilitates prostate cancer growth, metastasis, and drug resistance.

Highlights

  • Academic Editor: AlessandroProstate cancer is the second most common cancer in men, with global prostate cancer-related deaths exceeding 375,000 annually [1]

  • ICRT3 treatment has been shown to reduce tumor burden in the androgen-independent LNCaP-abl prostate cancer xenograft model [235]. These findings indicate that small molecule inhibitors that target β-catenin may show efficacy in patients with prostate cancer, further research is needed to identify which patient populations are likely to respond and to explore unique avenues for drug delivery to minimize adverse effects associated with systemic down-regulation of Wnt signaling

  • Oncogenic activation of the Wnt pathway plays a significant role in tumor growth, metastasis, and therapeutic resistance

Read more

Summary

Introduction

Prostate cancer is the second most common cancer in men, with global prostate cancer-related deaths exceeding 375,000 annually [1]. Wnt signaling is commonly activated in prostate cancer, metastatic prostate cancer, and clinical data has revealed oncogenic Wnt signaling is correlated with a high Gleason score, high prostate specific antigen (PSA) serum levels, early disease onset (

Wnt Signaling Pathway
Schematic canonical and non-canonical
Wnt Signaling and AR Crosstalk
Wnt Pathway Genetic Alterations in Prostate Cancer
Activation of the Wnt Pathway in Prostate Cancer
Deregulation of Intracellular Components
Deregulation of
APC Inactivation
DVL Deregulation
Upregulation of Wnt Pathway Transcription Factors
FZD Receptors
LGR Deregulation
LRP Deregulation
RYK Upregulation
RNF43 and ZNRF3 Deregulation
Wnt Ligands
Genetically Engineered Mouse Models (GEMMs) of Prostate Cancer
Human Prostate Cancer Xenograft Models
Organoids
Wnt Signaling and Prostate Cancer Metastasis
Targeting the Wnt Cascade to Treat Prostate Cancer
Inhibition of β-Catenin
Inhibition of Tankyrase1/2
Inhibition of Wnt Ligand Secretion
Inhibition of DKK1
Inhibition of ROR1
Wnt Pathway-Directed Therapies Yet to Be Explored in Prostate Cancer
Inhibition of RSPOs
Inhibition of sFRPs
Inhibition of FZDs
Findings
Conclusions
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call