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@article{1792166,
author = {Mahdal, Michal and Neradil, Jakub and Múdry, Peter and Paukovčeková, Silvia and Zambo, Iva and Urban, Jiří and Macsek, Peter and Pazourek, Lukáš and Tomáš, Tomáš and Veselská, Renata},
article_location = {Basel},
article_number = {14},
doi = {http://dx.doi.org/10.3390/cancers13143543},
keywords = {giant-cell tumor of bone; targeted treatment; sunitinib; PDGFR beta; denosumab; signaling},
language = {eng},
issn = {2072-6694},
journal = {Cancers},
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},
url = {https://www.mdpi.com/2072-6694/13/14/3543},
volume = {13},
year = {2021}
}
TY - JOUR
ID - 1792166
AU - Mahdal, Michal - Neradil, Jakub - Múdry, Peter - Paukovčeková, Silvia - Zambo, Iva - Urban, Jiří - Macsek, Peter - Pazourek, Lukáš - Tomáš, Tomáš - Veselská, Renata
PY - 2021
TI - 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
JF - Cancers
VL - 13
IS - 14
SP - 3543
EP - 3543
PB - MDPI
SN - 20726694
KW - giant-cell tumor of bone
KW - targeted treatment
KW - sunitinib
KW - PDGFR beta
KW - denosumab
KW - signaling
UR - https://www.mdpi.com/2072-6694/13/14/3543
N2 - 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. PDGFRβ 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 PDGFRβ.
ER -
MAHDAL, Michal, Jakub NERADIL, Peter MÚDRY, Silvia PAUKOVČEKOVÁ, Iva ZAMBO, Jiří URBAN, Peter MACSEK, Lukáš PAZOUREK, Tomáš TOMÁŠ a Renata VESELSKÁ. 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. \textit{Cancers}. Basel: MDPI, roč.~13, č.~14, s.~3543-3557. ISSN~2072-6694. doi:10.3390/cancers13143543. 2021.
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