The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion

Abstract Bromodomain and extraterminal domain (BET) proteins have emerged as therapeutic targets in multiple cancers, including the most common primary adult brain tumor glioblastoma (GBM). Although several BET inhibitors have entered clinical trials, few are brain penetrant. We have generated UM-00...

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Autores principales:	Anna M. Jermakowicz, Matthew J. Rybin, Robert K. Suter, Jann N. Sarkaria, Zane Zeier, Yangbo Feng, Nagi G. Ayad
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42bc0a0c7a934a7485fd2a2ac6e81440
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spelling	oai:doaj.org-article:42bc0a0c7a934a7485fd2a2ac6e814402021-12-05T12:13:56ZThe novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion10.1038/s41598-021-02584-62045-2322https://doaj.org/article/42bc0a0c7a934a7485fd2a2ac6e814402021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02584-6https://doaj.org/toc/2045-2322Abstract Bromodomain and extraterminal domain (BET) proteins have emerged as therapeutic targets in multiple cancers, including the most common primary adult brain tumor glioblastoma (GBM). Although several BET inhibitors have entered clinical trials, few are brain penetrant. We have generated UM-002, a novel brain penetrant BET inhibitor that reduces GBM cell proliferation in vitro and in a human cerebral brain organoid model. Since UM-002 is more potent than other BET inhibitors, it could potentially be developed for GBM treatment. Furthermore, UM-002 treatment reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors as measured by single cell RNA-sequencing. These studies suggest that BET inhibition alters the transcriptional landscape of GBM tumors, which has implications for designing combination therapies. Importantly, they also provide an integrated dataset that combines in vitro and ex vivo studies with in vivo single-cell RNA-sequencing to characterize a novel BET inhibitor in GBM.Anna M. JermakowiczMatthew J. RybinRobert K. SuterJann N. SarkariaZane ZeierYangbo FengNagi G. AyadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna M. Jermakowicz Matthew J. Rybin Robert K. Suter Jann N. Sarkaria Zane Zeier Yangbo Feng Nagi G. Ayad The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion
description	Abstract Bromodomain and extraterminal domain (BET) proteins have emerged as therapeutic targets in multiple cancers, including the most common primary adult brain tumor glioblastoma (GBM). Although several BET inhibitors have entered clinical trials, few are brain penetrant. We have generated UM-002, a novel brain penetrant BET inhibitor that reduces GBM cell proliferation in vitro and in a human cerebral brain organoid model. Since UM-002 is more potent than other BET inhibitors, it could potentially be developed for GBM treatment. Furthermore, UM-002 treatment reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors as measured by single cell RNA-sequencing. These studies suggest that BET inhibition alters the transcriptional landscape of GBM tumors, which has implications for designing combination therapies. Importantly, they also provide an integrated dataset that combines in vitro and ex vivo studies with in vivo single-cell RNA-sequencing to characterize a novel BET inhibitor in GBM.
format	article
author	Anna M. Jermakowicz Matthew J. Rybin Robert K. Suter Jann N. Sarkaria Zane Zeier Yangbo Feng Nagi G. Ayad
author_facet	Anna M. Jermakowicz Matthew J. Rybin Robert K. Suter Jann N. Sarkaria Zane Zeier Yangbo Feng Nagi G. Ayad
author_sort	Anna M. Jermakowicz
title	The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion
title_short	The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion
title_full	The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion
title_fullStr	The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion
title_full_unstemmed	The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion
title_sort	novel bet inhibitor um-002 reduces glioblastoma cell proliferation and invasion
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/42bc0a0c7a934a7485fd2a2ac6e81440
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The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion

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