The RANK-RANKL-OPG axis in dermatological malignancies: A systematic review

The receptor activator of nuclear factor kappa-B (RANK) and its ligand (RANKL) are key regulators in bone metabolism. Beyond its role in skeletal biology, RANKL has emerged as a mediator in skin immunity and tumorigenesis.

This systematic review evaluates current evidence regarding the RANK-RANKL-OPG axis in the development and treatment of skin tumors.

A comprehensive search was conducted across Scopus, Web of Science, PubMed, and the Cochrane Library using dermatology-related and axis-specific keywords. Articles were screened by title, abstract, and full text for relevance. Study quality was assessed through the Mixed Methods Appraisal Tool (MMAT). Data were synthesized narratively to evaluate the mechanistic role of the RANK-RANKL-OPG axis across tumor types, therapeutic outcomes were also descriptively analyzed where applicable.

A total of 27 studies were included. The results discussed the involvement of the RANK-RANKL-OPG axis role in melanoma, extramammary Paget's disease, cutaneous angiosarcoma, apocrine carcinoma, and Porokeratosis. This axis was found to contribute to immune evasion, angiogenesis, and metastasis in cutaneous malignancies. Furthermore, Denosumab, a RANKL-blocking agent, showed therapeutic potential in cutaneous related malignancies. However, the study is limited by a lack of clinical evidence.

The RANK-RANKL-OPG axis holds promise as a diagnostic and therapeutic target in dermatologic malignancies, warranting further clinical research.