The WNT/ROR Pathway in Cancer: From Signaling to Therapeutic Intervention

Area of Science:

• Oncology
• Molecular Biology
• Signal Transduction

Background:

• The WNT pathway is frequently dysregulated in human cancers.
• While β-catenin-dependent WNT signaling is well-studied, β-catenin-independent pathways like WNT/PCP and WNT/Ca2+ are also activated.
• Receptor tyrosine kinase-like orphan receptors (RORs) mediate WNT signaling and are increasingly recognized for their role in cancer.

Purpose of the Study:

• To review the structure, expression, and signaling of RORs in cancer.
• To explore the role of WNT/ROR signaling in tumor development and progression.
• To summarize current anti-ROR therapeutic strategies and their clinical potential.

Main Methods:

• Literature review of seminal findings on RORs in cancer.
• Analysis of ROR expression patterns in various tumor entities.
• Summary of preclinical and clinical studies on WNT/ROR targeted therapies.

Main Results:

• WNT/ROR signaling is linked to cancer cell proliferation, survival, invasion, and therapy resistance.
• RORs are overexpressed in many tumor types but largely absent in adult tissues, making them attractive therapeutic targets.
• Preclinical and early clinical studies show promising results for anti-ROR treatment approaches.

Conclusions:

• WNT/ROR signaling represents a significant driver of cancer progression.
• Targeting RORs offers a promising strategy for novel cancer therapies.
• Further research and clinical development are needed to overcome challenges in anti-ROR treatment.