Noncanonical Wnt as a prognostic marker in prostate cancer: “you can’t always get what you Wnt”

ABSTRACT

Introduction: Wnt signaling is important for normal development, cell proliferation, and cell differentiation. However, aberrations in the pathway can lead to tumorigenesis and cancer progression. Recent genome-wide studies have demonstrated the frequent occurrence of Wnt pathway alterations in prostate cancer. Although alterations in the canonical Wnt pathway in prostate cancer may have an impact on prognosis, recent studies suggest that the noncanonical Wnt pathway also plays an important role in disease progression and treatment resistance.

Areas covered: We review the literature with regard to the potential prognostic significance of noncanonical Wnt signaling in prostate cancer. After a brief overview of the canonical and noncanonical Wnt pathways, we discuss the preclinical and clinical evidence for activation of Wnt signaling in prostate cancer. We focus on clinical evidence for noncanonical Wnt pathway components to serve as potential prognostic biomarkers.

Expert opinion: Although many therapeutic options are available for men with prostate cancer, there remains an unmet need for prognostic and predictive biomarkers to precisely guide clinical management. Early evidence suggests that components of the noncanonical Wnt pathway may serve as prognostic biomarkers. However, prospective validation studies are necessary before these biomarkers can be routinely applied in the clinic.

KEYWORDS:

• Biomarkers
• noncanonical Wnt
• prostate cancer
• Wnt
• Wnt5a

Article Highlights

• The Wnt signaling pathway is frequently altered in prostate cancer and may play an important role in disease progression and treatment resistance.

• Wnt signaling is comprised of canonical ß-catenin dependent and noncanonical ß-catenin independent pathways.

• Both canonical and noncanonical Wnt pathways have been shown to be activated in prostate cancer, particularly in advanced disease.

• Alteration of noncanonical Wnt pathway components correlate with worse outcomes in metastatic prostate cancer and may have prognostic value in localized prostate cancer.

• Prospective validation studies are necessary before noncanonical Wnt biomarkers can be implemented in the clinic.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported in part by grants from the Prostate Cancer Foundation and the Swanson Family Award to the Mass General Cancer Center.