Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance

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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Main Authors: 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
Format: Article
Language:English
Published: Nature Publishing Group 2021-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-021-23463-8

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https://doi.org/10.1038/s41467-021-23463-8

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