Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer associated with high mortality. Merkel cell polyomavirus (MCV), discovered in 2008, is associated with ~80% of MCC. The MCV large tumor (LT) oncoprotein upregulates the cellular oncoprotein survivin through its conserved retinoblastoma prot...

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Autores principales:	Lindsay R Dresang, Anna Guastafierro, Reety Arora, Daniel Normolle, Yuan Chang, Patrick S Moore
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e7909d6eac544daa993c3a34efd7e948
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spelling	oai:doaj.org-article:e7909d6eac544daa993c3a34efd7e9482021-11-18T08:46:02ZResponse of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.1932-620310.1371/journal.pone.0080543https://doaj.org/article/e7909d6eac544daa993c3a34efd7e9482013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24260412/?tool=EBIhttps://doaj.org/toc/1932-6203Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer associated with high mortality. Merkel cell polyomavirus (MCV), discovered in 2008, is associated with ~80% of MCC. The MCV large tumor (LT) oncoprotein upregulates the cellular oncoprotein survivin through its conserved retinoblastoma protein-binding motif. We confirm here that YM155, a survivin suppressor, is cytotoxic to MCV-positive MCC cells in vitro at nanomolar levels. Mouse survival was significantly improved for NOD-Scid-Gamma mice treated with YM155 in a dose and duration dependent manner for 3 of 4 MCV-positive MCC xenografts. One MCV-positive MCC xenograft (MS-1) failed to significantly respond to YM155, which corresponds with in vitro dose-response activity. Combination treatment of YM155 with other chemotherapeutics resulted in additive but not synergistic cell killing of MCC cell lines in vitro. These results suggest that survivin targeting is a promising therapeutic approach for most but not all MCV-positive MCCs.Lindsay R DresangAnna GuastafierroReety AroraDaniel NormolleYuan ChangPatrick S MoorePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80543 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lindsay R Dresang Anna Guastafierro Reety Arora Daniel Normolle Yuan Chang Patrick S Moore Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.
description	Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer associated with high mortality. Merkel cell polyomavirus (MCV), discovered in 2008, is associated with ~80% of MCC. The MCV large tumor (LT) oncoprotein upregulates the cellular oncoprotein survivin through its conserved retinoblastoma protein-binding motif. We confirm here that YM155, a survivin suppressor, is cytotoxic to MCV-positive MCC cells in vitro at nanomolar levels. Mouse survival was significantly improved for NOD-Scid-Gamma mice treated with YM155 in a dose and duration dependent manner for 3 of 4 MCV-positive MCC xenografts. One MCV-positive MCC xenograft (MS-1) failed to significantly respond to YM155, which corresponds with in vitro dose-response activity. Combination treatment of YM155 with other chemotherapeutics resulted in additive but not synergistic cell killing of MCC cell lines in vitro. These results suggest that survivin targeting is a promising therapeutic approach for most but not all MCV-positive MCCs.
format	article
author	Lindsay R Dresang Anna Guastafierro Reety Arora Daniel Normolle Yuan Chang Patrick S Moore
author_facet	Lindsay R Dresang Anna Guastafierro Reety Arora Daniel Normolle Yuan Chang Patrick S Moore
author_sort	Lindsay R Dresang
title	Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.
title_short	Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.
title_full	Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.
title_fullStr	Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.
title_full_unstemmed	Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.
title_sort	response of merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e7909d6eac544daa993c3a34efd7e948
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_version_	1718421356976013312

Response of Merkel cell polyomavirus-positive merkel cell carcinoma xenografts to a survivin inhibitor.

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