• Diego De Leon-Oliva, Silvestra Barrena-Blázquez, Laura Jiménez-Álvarez, Oscar Fraile-Martinez, Cielo García-Montero, Laura López-González, Diego Torres-Carranza, Luis M García-Puente, Sara T Carranza, Miguel Ángel Álvarez-Mon, Melchor Álvarez-Mon, Raul Diaz, and Miguel A Ortega.
• Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain.
• Medicina (Kaunas). 2023 Sep 30; 59 (10).

AbstractThe RANK-RANKL-OPG system is a complex signaling pathway that plays a critical role in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL is a ligand that binds to RANK, a receptor expressed on osteoclasts, dendritic cells, T cells, and other cells. RANKL signaling promotes osteoclast differentiation and activation, which leads to bone resorption. OPG is a decoy receptor that binds to RANKL and inhibits its signaling. In cancer cells, RANKL expression is often increased, which can lead to increased bone resorption and the development of bone metastases. RANKL-neutralizing antibodies, such as denosumab, have been shown to be effective in the treatment of skeletal-related events, including osteoporosis or bone metastases, and cancer. This review will provide a comprehensive overview of the functions of the RANK-RANKL-OPG system in bone metabolism, mammary epithelial cells, immune function, and cancer, together with the potential therapeutic implications of the RANK-RANKL pathway for cancer management.

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