New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling
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 sig...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/14/3543 |
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| author | Michal Mahdal Jakub Neradil Peter Mudry Silvia Paukovcekova Iva Staniczkova Zambo Jiri Urban Peter Macsek Lukas Pazourek Tomas Tomas Renata Veselska |
| author_facet | Michal Mahdal Jakub Neradil Peter Mudry Silvia Paukovcekova Iva Staniczkova Zambo Jiri Urban Peter Macsek Lukas Pazourek Tomas Tomas Renata Veselska |
| author_sort | Michal Mahdal |
| collection | DOAJ |
| description | 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 <i>in vitro</i>. 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. |
| first_indexed | 2024-03-10T09:43:39Z |
| format | Article |
| id | doaj.art-0359ddf0f0ab42c5a01569643702929b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:43:39Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0359ddf0f0ab42c5a01569643702929b2023-11-22T03:25:04ZengMDPI AGCancers2072-66942021-07-011314354310.3390/cancers13143543New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ SignalingMichal Mahdal0Jakub Neradil1Peter Mudry2Silvia Paukovcekova3Iva Staniczkova Zambo4Jiri Urban5Peter Macsek6Lukas Pazourek7Tomas Tomas8Renata Veselska9First Department of Orthopedic Surgery, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, 65691 Brno, Czech RepublicLaboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech RepublicInternational Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech RepublicLaboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech RepublicInternational Clinical Research Center, St. Anne’s University Hospital, 65691 Brno, Czech RepublicDepartment of Chemistry, Faculty of Science, Masaryk University, 61137 Brno, Czech RepublicLaboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech RepublicFirst Department of Orthopedic Surgery, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, 65691 Brno, Czech RepublicFirst Department of Orthopedic Surgery, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, 65691 Brno, Czech RepublicLaboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech RepublicGiant-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 <i>in vitro</i>. 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.https://www.mdpi.com/2072-6694/13/14/3543giant-cell tumor of bonetargeted treatmentsunitinibPDGFR betadenosumabsignaling |
| spellingShingle | Michal Mahdal Jakub Neradil Peter Mudry Silvia Paukovcekova Iva Staniczkova Zambo Jiri Urban Peter Macsek Lukas Pazourek Tomas Tomas Renata Veselska New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling Cancers giant-cell tumor of bone targeted treatment sunitinib PDGFR beta denosumab signaling |
| title | New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling |
| title_full | New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling |
| title_fullStr | New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling |
| title_full_unstemmed | New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling |
| title_short | New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRβ Signaling |
| title_sort | new target for precision medicine treatment of giant cell tumor of bone sunitinib is effective in the treatment of neoplastic stromal cells with activated pdgfrβ signaling |
| topic | giant-cell tumor of bone targeted treatment sunitinib PDGFR beta denosumab signaling |
| url | https://www.mdpi.com/2072-6694/13/14/3543 |
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