Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair

Zonneville et al. show that p53 mutant cancers express high levels of the Base Excision Repair (BER) pathway and that deoxyuridine analogues induce DNA damage in p53-mutant TNBC cells. They exploit this genetic liability for therapeutic purposes using a combination of fluorinated deoxyuridine analog...

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Autores principales:	Justin Zonneville, Moyi Wang, Mohammed M. Alruwaili, Brandon Smith, Megan Melnick, Kevin H. Eng, Thomas Melendy, Ben Ho Park, Renuka Iyer, Christos Fountzilas, Andrei V. Bakin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/82a83cc457434b04a6a0abf6527d94ee
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spelling	oai:doaj.org-article:82a83cc457434b04a6a0abf6527d94ee2021-12-02T16:09:41ZSelective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair10.1038/s42003-021-02370-02399-3642https://doaj.org/article/82a83cc457434b04a6a0abf6527d94ee2021-07-01T00:00:00Zhttps://doi.org/10.1038/s42003-021-02370-0https://doaj.org/toc/2399-3642Zonneville et al. show that p53 mutant cancers express high levels of the Base Excision Repair (BER) pathway and that deoxyuridine analogues induce DNA damage in p53-mutant TNBC cells. They exploit this genetic liability for therapeutic purposes using a combination of fluorinated deoxyuridine analogues and PARP1 inhibitors to target the BER pathway, inducing cytotoxicity and suppressing tumor growth in mice.Justin ZonnevilleMoyi WangMohammed M. AlruwailiBrandon SmithMegan MelnickKevin H. EngThomas MelendyBen Ho ParkRenuka IyerChristos FountzilasAndrei V. BakinNature PortfolioarticleBiology (General)QH301-705.5ENCommunications Biology, Vol 4, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Justin Zonneville Moyi Wang Mohammed M. Alruwaili Brandon Smith Megan Melnick Kevin H. Eng Thomas Melendy Ben Ho Park Renuka Iyer Christos Fountzilas Andrei V. Bakin Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair
description	Zonneville et al. show that p53 mutant cancers express high levels of the Base Excision Repair (BER) pathway and that deoxyuridine analogues induce DNA damage in p53-mutant TNBC cells. They exploit this genetic liability for therapeutic purposes using a combination of fluorinated deoxyuridine analogues and PARP1 inhibitors to target the BER pathway, inducing cytotoxicity and suppressing tumor growth in mice.
format	article
author	Justin Zonneville Moyi Wang Mohammed M. Alruwaili Brandon Smith Megan Melnick Kevin H. Eng Thomas Melendy Ben Ho Park Renuka Iyer Christos Fountzilas Andrei V. Bakin
author_facet	Justin Zonneville Moyi Wang Mohammed M. Alruwaili Brandon Smith Megan Melnick Kevin H. Eng Thomas Melendy Ben Ho Park Renuka Iyer Christos Fountzilas Andrei V. Bakin
author_sort	Justin Zonneville
title	Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair
title_short	Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair
title_full	Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair
title_fullStr	Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair
title_full_unstemmed	Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair
title_sort	selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in dna repair
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/82a83cc457434b04a6a0abf6527d94ee
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Selective therapeutic strategy for p53-deficient cancer by targeting dysregulation in DNA repair

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