Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance
Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP in...
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Nature Portfolio
2021
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oai:doaj.org-article:a5462d8522964b13a5f79a9e1b35250a2021-12-02T16:04:21ZPolθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance10.1038/s41467-021-23463-82041-1723https://doaj.org/article/a5462d8522964b13a5f79a9e1b35250a2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-23463-8https://doaj.org/toc/2041-1723Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP inhibitor resistance caused by 53BP1/Shieldin pathway defects.Diana ZatreanuHelen M. R. RobinsonOmar AlkhatibMarie BoursierHarry FinchLerin GeoDiego GrandeVera GrinkevichRobert A. HealdSophie LangdonJayesh MajithiyaClaire McWhirterNiall M. B. MartinShaun MooreJoana NevesEeson RajendraMarco RanzaniTheresia SchaedlerMartin StockleyKimberley WigginsRachel BroughSandhya SridharAditi GulatiNan ShaoLuned M. BadderDaniela NovoEleanor G. KnightRebecca MarlowSyed HaiderElsa CallenGraeme HewittJoost SchimmelRemko PrevoChristina AlliAmanda FerdinandCameron BellPeter BlencoweChris BotMathew CalderMark CharlesJayne CurryTennyson EkwuruKatherine EwingsWojciech KrajewskiEllen MacDonaldHollie McCarronLeon PangChris PedderLaurent RigoreauMartin SwarbrickEd WheatleySimon WillisAi Ching WongAndre NussenzweigMarcel TijstermanAndrew TuttSimon J. BoultonGeoff S. HigginsStephen J. PettittGraeme C. M. SmithChristopher J. LordNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
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Science Q Diana Zatreanu Helen M. R. Robinson Omar Alkhatib Marie Boursier Harry Finch Lerin Geo Diego Grande Vera Grinkevich Robert A. Heald Sophie Langdon Jayesh Majithiya Claire McWhirter Niall M. B. Martin Shaun Moore Joana Neves Eeson Rajendra Marco Ranzani Theresia Schaedler Martin Stockley Kimberley Wiggins Rachel Brough Sandhya Sridhar Aditi Gulati Nan Shao Luned M. Badder Daniela Novo Eleanor G. Knight Rebecca Marlow Syed Haider Elsa Callen Graeme Hewitt Joost Schimmel Remko Prevo Christina Alli Amanda Ferdinand Cameron Bell Peter Blencowe Chris Bot Mathew Calder Mark Charles Jayne Curry Tennyson Ekwuru Katherine Ewings Wojciech Krajewski Ellen MacDonald Hollie McCarron Leon Pang Chris Pedder Laurent Rigoreau Martin Swarbrick Ed Wheatley Simon Willis Ai Ching Wong Andre Nussenzweig Marcel Tijsterman Andrew Tutt Simon J. Boulton Geoff S. Higgins Stephen J. Pettitt Graeme C. M. Smith Christopher J. Lord Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance |
| description |
Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP inhibitor resistance caused by 53BP1/Shieldin pathway defects. |
| format |
article |
| author |
Diana Zatreanu Helen M. R. Robinson Omar Alkhatib Marie Boursier Harry Finch Lerin Geo Diego Grande Vera Grinkevich Robert A. Heald Sophie Langdon Jayesh Majithiya Claire McWhirter Niall M. B. Martin Shaun Moore Joana Neves Eeson Rajendra Marco Ranzani Theresia Schaedler Martin Stockley Kimberley Wiggins Rachel Brough Sandhya Sridhar Aditi Gulati Nan Shao Luned M. Badder Daniela Novo Eleanor G. Knight Rebecca Marlow Syed Haider Elsa Callen Graeme Hewitt Joost Schimmel Remko Prevo Christina Alli Amanda Ferdinand Cameron Bell Peter Blencowe Chris Bot Mathew Calder Mark Charles Jayne Curry Tennyson Ekwuru Katherine Ewings Wojciech Krajewski Ellen MacDonald Hollie McCarron Leon Pang Chris Pedder Laurent Rigoreau Martin Swarbrick Ed Wheatley Simon Willis Ai Ching Wong Andre Nussenzweig Marcel Tijsterman Andrew Tutt Simon J. Boulton Geoff S. Higgins Stephen J. Pettitt Graeme C. M. Smith Christopher J. Lord |
| author_facet |
Diana Zatreanu Helen M. R. Robinson Omar Alkhatib Marie Boursier Harry Finch Lerin Geo Diego Grande Vera Grinkevich Robert A. Heald Sophie Langdon Jayesh Majithiya Claire McWhirter Niall M. B. Martin Shaun Moore Joana Neves Eeson Rajendra Marco Ranzani Theresia Schaedler Martin Stockley Kimberley Wiggins Rachel Brough Sandhya Sridhar Aditi Gulati Nan Shao Luned M. Badder Daniela Novo Eleanor G. Knight Rebecca Marlow Syed Haider Elsa Callen Graeme Hewitt Joost Schimmel Remko Prevo Christina Alli Amanda Ferdinand Cameron Bell Peter Blencowe Chris Bot Mathew Calder Mark Charles Jayne Curry Tennyson Ekwuru Katherine Ewings Wojciech Krajewski Ellen MacDonald Hollie McCarron Leon Pang Chris Pedder Laurent Rigoreau Martin Swarbrick Ed Wheatley Simon Willis Ai Ching Wong Andre Nussenzweig Marcel Tijsterman Andrew Tutt Simon J. Boulton Geoff S. Higgins Stephen J. Pettitt Graeme C. M. Smith Christopher J. Lord |
| author_sort |
Diana Zatreanu |
| title |
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance |
| title_short |
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance |
| title_full |
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance |
| title_fullStr |
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance |
| title_full_unstemmed |
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance |
| title_sort |
polθ inhibitors elicit brca-gene synthetic lethality and target parp inhibitor resistance |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/a5462d8522964b13a5f79a9e1b35250a |
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