title: Giant-cell tumor of bone, anti-RANKL therapy.
abstract: Giant-cell tumor of bone (GCTB) is a rare osteolytic tumor of the bone. Although classified as a benign tumor, GCTB is characterized by local aggressiveness and risk of local recurrence. In addition, GTCB can in some cases lead to the development of so-called 'benign' chest metastases. Surgical resection by intralesional curettage with high-speed burring and polymethylmethacrylate cement is the standard treatment for resectable tumors. In cases of metastatic or unresectable disease (when planned surgical procedure is impossible or would result in severe morbidity), medical treatments such as cytotoxic chemotherapy or interferon-α have limited efficacy. Bisphosphonates have been proposed as a therapeutic option to reduce osteoclast activity. In bone, various pathological states may result from an imbalance in the RANK (receptor activator of nuclear factor kappa-B)/RANKL (receptor activator of nuclear factor kappa-B ligand)/OPG (osteoprotegerin) pathway. Involvement of the RANKL pathway in pathogenesis of GCTB was first proposed in 2000. Denosumab is a fully human monoclonal antibody that binds and inhibits RANKL, thereby preventing the activation of the RANK pathway. As it showed the possibility to counteract osteoclast activation in GCTB and prevent the known physiopathological role of RANKL, denosumab has been under evaluation in the clinic as a treatment for GCTB since 2005. Results of a first Phase II trial demonstrate the therapeutic potential of denosumab to inhibit progressive bone destruction and metastatic progression in patients with unsalvageable giant-cell tumor (GCT), and have also provided key insights into the biology of GCT. Denosumab is currently a therapeutic option for patients with unresectable GCTB but its place in the global therapeutic strategy has not yet been defined.
authors.affiliation: Cancer Research Center of Lyon (CRCL), Department of 'Immunity, Virus and Microenvironnement', UMR INSERM 1052-CNRS 5286, Leon Berard Cancer Center , Lyon, France .
authors.forename: Armelle
authors.initials: A
authors.lastname: Dufresne
authors.affiliation: Medical Oncology Department, Leon Berard Cancer Center , Lyon, France .
authors.forename: Olfa
authors.initials: O
authors.lastname: Derbel
authors.affiliation: Cancer Research Center of Lyon (CRCL), Department of 'Immunity, Virus and Microenvironnement', UMR INSERM 1052-CNRS 5286, Leon Berard Cancer Center , Lyon, France . ; Medical Oncology Department, Leon Berard Cancer Center , Lyon, France .
authors.forename: Philippe
authors.initials: P
authors.lastname: Cassier
authors.affiliation: Surgery Department, Edouard Herriot Hospital , Lyon, France .
authors.forename: Gualter
authors.initials: G
authors.lastname: Vaz
authors.affiliation: Pathology Department, Leon Berard Cancer Center , Lyon, France .
authors.forename: Anne-Valérie
authors.initials: AV
authors.lastname: Decouvelaere
authors.affiliation: Cancer Research Center of Lyon (CRCL), Department of 'Immunity, Virus and Microenvironnement', UMR INSERM 1052-CNRS 5286, Leon Berard Cancer Center , Lyon, France . ; Medical Oncology Department, Leon Berard Cancer Center , Lyon, France .
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay