Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.

Studies in diverse organisms have revealed a surprising depth to the evolutionary conservation of genetic modules. For example, a systematic analysis of such conserved modules has recently shown that genes in yeast that maintain cell walls have been repurposed in vertebrates to regulate vein and art...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hye Ji Cha, Michelle Byrom, Paul E Mead, Andrew D Ellington, John B Wallingford, Edward M Marcotte
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d54a379b43ab4f1ca5f3ee50970cc441
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d54a379b43ab4f1ca5f3ee50970cc441
record_format	dspace
spelling	oai:doaj.org-article:d54a379b43ab4f1ca5f3ee50970cc4412021-11-18T05:36:33ZEvolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.1544-91731545-788510.1371/journal.pbio.1001379https://doaj.org/article/d54a379b43ab4f1ca5f3ee50970cc4412012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927795/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Studies in diverse organisms have revealed a surprising depth to the evolutionary conservation of genetic modules. For example, a systematic analysis of such conserved modules has recently shown that genes in yeast that maintain cell walls have been repurposed in vertebrates to regulate vein and artery growth. We reasoned that by analyzing this particular module, we might identify small molecules targeting the yeast pathway that also act as angiogenesis inhibitors suitable for chemotherapy. This insight led to the finding that thiabendazole, an orally available antifungal drug in clinical use for 40 years, also potently inhibits angiogenesis in animal models and in human cells. Moreover, in vivo time-lapse imaging revealed that thiabendazole reversibly disassembles newly established blood vessels, marking it as vascular disrupting agent (VDA) and thus as a potential complementary therapeutic for use in combination with current anti-angiogenic therapies. Importantly, we also show that thiabendazole slows tumor growth and decreases vascular density in preclinical fibrosarcoma xenografts. Thus, an exploration of the evolutionary repurposing of gene networks has led directly to the identification of a potential new therapeutic application for an inexpensive drug that is already approved for clinical use in humans.Hye Ji ChaMichelle ByromPaul E MeadAndrew D EllingtonJohn B WallingfordEdward M MarcottePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 10, Iss 8, p e1001379 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Hye Ji Cha Michelle Byrom Paul E Mead Andrew D Ellington John B Wallingford Edward M Marcotte Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.
description	Studies in diverse organisms have revealed a surprising depth to the evolutionary conservation of genetic modules. For example, a systematic analysis of such conserved modules has recently shown that genes in yeast that maintain cell walls have been repurposed in vertebrates to regulate vein and artery growth. We reasoned that by analyzing this particular module, we might identify small molecules targeting the yeast pathway that also act as angiogenesis inhibitors suitable for chemotherapy. This insight led to the finding that thiabendazole, an orally available antifungal drug in clinical use for 40 years, also potently inhibits angiogenesis in animal models and in human cells. Moreover, in vivo time-lapse imaging revealed that thiabendazole reversibly disassembles newly established blood vessels, marking it as vascular disrupting agent (VDA) and thus as a potential complementary therapeutic for use in combination with current anti-angiogenic therapies. Importantly, we also show that thiabendazole slows tumor growth and decreases vascular density in preclinical fibrosarcoma xenografts. Thus, an exploration of the evolutionary repurposing of gene networks has led directly to the identification of a potential new therapeutic application for an inexpensive drug that is already approved for clinical use in humans.
format	article
author	Hye Ji Cha Michelle Byrom Paul E Mead Andrew D Ellington John B Wallingford Edward M Marcotte
author_facet	Hye Ji Cha Michelle Byrom Paul E Mead Andrew D Ellington John B Wallingford Edward M Marcotte
author_sort	Hye Ji Cha
title	Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.
title_short	Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.
title_full	Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.
title_fullStr	Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.
title_full_unstemmed	Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.
title_sort	evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d54a379b43ab4f1ca5f3ee50970cc441
work_keys_str_mv	AT hyejicha evolutionarilyrepurposednetworksrevealthewellknownantifungaldrugthiabendazoletobeanovelvasculardisruptingagent AT michellebyrom evolutionarilyrepurposednetworksrevealthewellknownantifungaldrugthiabendazoletobeanovelvasculardisruptingagent AT paulemead evolutionarilyrepurposednetworksrevealthewellknownantifungaldrugthiabendazoletobeanovelvasculardisruptingagent AT andrewdellington evolutionarilyrepurposednetworksrevealthewellknownantifungaldrugthiabendazoletobeanovelvasculardisruptingagent AT johnbwallingford evolutionarilyrepurposednetworksrevealthewellknownantifungaldrugthiabendazoletobeanovelvasculardisruptingagent AT edwardmmarcotte evolutionarilyrepurposednetworksrevealthewellknownantifungaldrugthiabendazoletobeanovelvasculardisruptingagent
_version_	1718424943120613376

Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.

Ejemplares similares