New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFR beta Signaling

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F21%3A00074454" target="_blank" >RIV/00159816:_____/21:00074454 - isvavai.cz</a>

Alternative codes found

RIV/65269705:_____/21:00074454

Result on the web

<a href="https://www.mdpi.com/2072-6694/13/14/3543" target="_blank" >https://www.mdpi.com/2072-6694/13/14/3543</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers13143543" target="_blank" >10.3390/cancers13143543</a>

Result language

angličtina

Original language name

New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFR beta Signaling

Original language description

Simple Summary The purpose of this study was to analyze differential cell signaling in response to denosumab treatment to identify and subsequently inhibit molecular targets in the neoplastic stromal cell population, which poses a risk for tumor recurrence. Using phosphoprotein arrays, a distinct signaling profile was detected in GCTB tissues treated with denosumab, a specific RANKL antibody, which coincided with the RTK profile in derived cell lines. PDGFR beta was selected as a promising receptor target, and its inhibition by the small-molecule inhibitor sunitinib resulted in potent inhibition of cell proliferation in vitro. The addition of sunitinib to denosumab resulted in the disappearance of both multinuclear giant cells and neoplastic stromal cells, as reported here. Thus, sunitinib could become an effective addition to denosumab in the treatment of GCTB with activated PDGFR beta. 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 (PDGFR beta) 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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancers

ISSN

2072-6694

e-ISSN

—

Volume of the periodical

13

Issue of the periodical within the volume

14

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

3543

UT code for WoS article

000677361200001

EID of the result in the Scopus database

2-s2.0-85110129266