Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter

Abstract Adverse side effects of cancer agents are of great concern in the context of childhood tumors where they can reduce the quality of life in young patients and cause life-long adverse effects. Synergistic drug combinations can lessen potential toxic side effects through lower dosing and simul...

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Autores principales:	Branka Radic-Sarikas, Melinda Halasz, Kilian V. M. Huber, Georg E. Winter, Kalliopi P. Tsafou, Theodore Papamarkou, Søren Brunak, Walter Kolch, Giulio Superti-Furga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69692b39268b4938b59ac45022e3640d
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spelling	oai:doaj.org-article:69692b39268b4938b59ac45022e3640d2021-12-02T15:04:52ZLapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter10.1038/s41598-017-03129-62045-2322https://doaj.org/article/69692b39268b4938b59ac45022e3640d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03129-6https://doaj.org/toc/2045-2322Abstract Adverse side effects of cancer agents are of great concern in the context of childhood tumors where they can reduce the quality of life in young patients and cause life-long adverse effects. Synergistic drug combinations can lessen potential toxic side effects through lower dosing and simultaneously help to overcome drug resistance. Neuroblastoma is the most common cancer in infancy and extremely heterogeneous in clinical presentation and features. Applying a systematic pairwise drug combination screen we observed a highly potent synergy in neuroblastoma cells between the EGFR kinase inhibitor lapatinib and the anticancer compound YM155 that is preserved across several neuroblastoma variants. Mechanistically, the synergy was based on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is frequently expressed in resistant neuroblastoma cells, which allowed prolonged and elevated cytotoxicity of YM155. In addition, the drug combination (i.e. lapatinib plus YM155) decreased neuroblastoma tumor size in an in vivo model.Branka Radic-SarikasMelinda HalaszKilian V. M. HuberGeorg E. WinterKalliopi P. TsafouTheodore PapamarkouSøren BrunakWalter KolchGiulio Superti-FurgaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Branka Radic-Sarikas Melinda Halasz Kilian V. M. Huber Georg E. Winter Kalliopi P. Tsafou Theodore Papamarkou Søren Brunak Walter Kolch Giulio Superti-Furga Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter
description	Abstract Adverse side effects of cancer agents are of great concern in the context of childhood tumors where they can reduce the quality of life in young patients and cause life-long adverse effects. Synergistic drug combinations can lessen potential toxic side effects through lower dosing and simultaneously help to overcome drug resistance. Neuroblastoma is the most common cancer in infancy and extremely heterogeneous in clinical presentation and features. Applying a systematic pairwise drug combination screen we observed a highly potent synergy in neuroblastoma cells between the EGFR kinase inhibitor lapatinib and the anticancer compound YM155 that is preserved across several neuroblastoma variants. Mechanistically, the synergy was based on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is frequently expressed in resistant neuroblastoma cells, which allowed prolonged and elevated cytotoxicity of YM155. In addition, the drug combination (i.e. lapatinib plus YM155) decreased neuroblastoma tumor size in an in vivo model.
format	article
author	Branka Radic-Sarikas Melinda Halasz Kilian V. M. Huber Georg E. Winter Kalliopi P. Tsafou Theodore Papamarkou Søren Brunak Walter Kolch Giulio Superti-Furga
author_facet	Branka Radic-Sarikas Melinda Halasz Kilian V. M. Huber Georg E. Winter Kalliopi P. Tsafou Theodore Papamarkou Søren Brunak Walter Kolch Giulio Superti-Furga
author_sort	Branka Radic-Sarikas
title	Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter
title_short	Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter
title_full	Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter
title_fullStr	Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter
title_full_unstemmed	Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter
title_sort	lapatinib potentiates cytotoxicity of ym155 in neuroblastoma via inhibition of the abcb1 efflux transporter
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/69692b39268b4938b59ac45022e3640d
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Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter

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