Giant-cell tumor of bone (GCTB) is an intermediate type of primary bone tumor characterized by locally aggressive growth with metastatic potential. The aim of this study was to identify new druggable targets among the cell signaling molecules involved in GCTB tumorigenesis. Profiles of activated signaling proteins in fresh-frozen tumor samples and tumor-derived cell lines were determined using phosphoprotein arrays. Analysis of the obtained data revealed epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor beta (PDGFRβ) as potential targets, but only the PDGFR inhibitor sunitinib caused a considerable decrease in stromal cell viability in vitro. Furthermore, in the case of a 17-year-old patient suffering from GCTB, we showed that the addition of sunitinib to the standard treatment of GCTB with the monoclonal antibody denosumab resulted in the complete depletion of multinucleated giant cells and mononuclear stromal cells in the tumor tissue. To summarize, the obtained data showed that a specific receptor tyrosine kinase (RTK) signaling pattern is activated in GCTB cells and plays an important role in the regulation of cell proliferation. Thus, activated RTKs and their downstream signaling pathways represent useful targets for precision treatment with low-molecular-weight inhibitors or with other types of modern biological therapy.

1st Department of Orthopedic Surgery St Anne's University Hospital and Faculty of Medicine Masaryk University 65691 Brno Czech Republic

1st Pathology Department St Anne's University Hospital and Faculty of Medicine Masaryk University 65691 Brno Czech Republic

Department of Chemistry Faculty of Science Masaryk University 61137 Brno Czech Republic

Department of Pediatric Oncology University Hospital Brno and Faculty of Medicine Masaryk University 66263 Brno Czech Republic

International Clinical Research Center St Anne's University Hospital 65691 Brno Czech Republic

Laboratory of Tumor Biology Department of Experimental Biology Faculty of Science Masaryk University 61137 Brno Czech Republic

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Combined Proximal Radius Reconstruction Following Resection for Oncological Indication

Proximal Tibia Tumour Location and Curettage Are Major Risk Factors of Local Recurrence in Giant Cell Tumour of Bone

Total elbow replacement for giant-cell tumor of bone after denosumab treatment: a case report