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.

Basic information

Original 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 PDGFRβ Signaling

Authors

MAHDAL, Michal (203 Czech Republic, belonging to the institution), Jakub NERADIL (203 Czech Republic, belonging to the institution), Peter MÚDRY (203 Czech Republic, belonging to the institution), Silvia PAUKOVČEKOVÁ (703 Slovakia, belonging to the institution), Iva ZAMBO (203 Czech Republic, belonging to the institution), Jiří URBAN (203 Czech Republic, belonging to the institution), Peter MACSEK (703 Slovakia, belonging to the institution), Lukáš PAZOUREK (203 Czech Republic, belonging to the institution), Tomáš TOMÁŠ (203 Czech Republic, belonging to the institution) and Renata VESELSKÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cancers, Basel, MDPI, 2021, 2072-6694

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.575

RIV identification code

RIV/00216224:14310/21:00120142

Organization unit

Faculty of Science

DOI

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

UT WoS

000677361200001

Keywords in English

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

Abstract

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.

Links

MUNI/A/1477/2018, interní kód MU

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

Investor: Masaryk University, Category A

NV16-34083A, research and development project

Name: 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 and 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, vol. 13, No 14, p. 3543-3557. ISSN 2072-6694. Available from: 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 and 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, vol.~13, No~14, p.~3543-3557. ISSN~2072-6694. Available from: https://dx.doi.org/10.3390/cancers13143543.

Detailed Information on Publication Record