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

J 2021

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

MAHDAL, Michal, Jakub NERADIL, Peter MÚDRY, Silvia PAUKOVČEKOVÁ, Iva ZAMBO et. al.

Základní údaje

Originální název

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

Autoři

MAHDAL, Michal (203 Česká republika, domácí), Jakub NERADIL (203 Česká republika, domácí), Peter MÚDRY (203 Česká republika, domácí), Silvia PAUKOVČEKOVÁ (703 Slovensko, domácí), Iva ZAMBO (203 Česká republika, domácí), Jiří URBAN (203 Česká republika, domácí), Peter MACSEK (703 Slovensko, domácí), Lukáš PAZOUREK (203 Česká republika, domácí), Tomáš TOMÁŠ (203 Česká republika, domácí) a Renata VESELSKÁ (203 Česká republika, garant, domácí)

Vydání

Cancers, Basel, MDPI, 2021, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.575

Kód RIV

RIV/00216224:14310/21:00120142

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.3390/cancers13143543

UT WoS

000677361200001

Klíčová slova anglicky

giant-cell tumor of bone; targeted treatment; sunitinib; PDGFR beta; denosumab; signaling

Štítky

14110112, 14110123, 14110321, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 16. 11. 2021 15:48, Mgr. Marie Šípková, DiS.

Anotace

V originále

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.

Návaznosti

MUNI/A/1477/2018, interní kód MU

Název: Zkoumání účinku denosumabu na obrovskobuněčný kostní nádor v laboratorních podmínkách

Investor: Masarykova univerzita, Zkoumání účinku denosumabu na obrovskobuněčný kostní nádor v laboratorních podmínkách, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

NV16-34083A, projekt VaV

Název: Receptorové tyrozinkinázy a navazující signální dráhy jako potenciální cíle léčby refrakterních solidních nádorů dětského věku

Citovat

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. Cancers. Basel: MDPI, 2021, roč. 13, č. 14, s. 3543-3557. ISSN 2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers13143543.

@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, 2021, roč.~13, č.~14, s.~3543-3557. ISSN~2072-6694. Dostupné z: https://dx.doi.org/10.3390/cancers13143543.

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