AI Article Synopsis

  • Giant-cell tumor of bone (GCTB) is a type of bone tumor that grows aggressively and can spread, prompting researchers to find new drug targets for treatment.
  • The study used phosphoprotein arrays on tumor samples to identify activated signaling proteins, highlighting EGFR and PDGFRβ as potential targets, with sunitinib showing notable effectiveness in reducing stromal cell viability.
  • In a case study of a 17-year-old patient, combining sunitinib with denosumab led to the complete elimination of problematic tumor cells, suggesting targeted therapies could improve GCTB treatment outcomes.

Article Abstract

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 . 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305892PMC
http://dx.doi.org/10.3390/cancers13143543DOI Listing

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