title: Antineoplastic activity of zoledronic acid and denosumab.
abstract: Cancer patients suffer from cancer-induced bone pain, hypercalcemia, and reduced quality of life caused by pathological fractures. Many of these complications related to cancer can be treated, or at least controlled, using new anticancer agents. Recently, two agents used initially to treat osteoporosis demonstrated direct and indirect anticancer activity. In this review, we summarize current knowledge about direct and indirect anticancer activity of zoledronic acid (a third-generation bisphosphonate), and denosumab antibody against RANKL. Zoledronic acid influences the proliferation and viability of tumor cells in vitro, and effectively reduces tumor burden, tumor-induced pain, and tumor growth in vivo. Denosumab is a fully human monoclonal antibody preventing the binding of RANKL to its receptor on osteoclasts' membrane, and through this mechanism inhibits the resorption of the bone. Furthermore, this agent demonstrates direct anticancer activity through the RANKL signaling pathway. Because of these features both drugs may gain broader application for the treatment of cancer patients. However, further pre-clinical and clinical evaluation is needed for both agents to fully assess the antineoplastic mechanisms of activity of both agents.
authors.affiliation: Department of Medicine, University of Illinois at Chicago, 909 S. Wolcott, Chicago, IL 60612, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Zwolak
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000069448:Denosumab; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid
keywords: Zoledronic acid; anticancer therapy; denosumab; review; tumor growth