The DNA polymerase Polθ is synthetic lethal with homologous-recombination deficiency, but a lack of specific targeting compounds has limited its therapeutic potential. Two studies now describe first-in-class inhibitors of Polθ with in vivo efficacy and thus provide alternative therapeutic approaches to PARP inhibitors for cancers deficient in homologous recombination.
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Acknowledgements
Laboratory funding is from the Swedish Cancer Society (CAN2018/0658), the Swedish Children’s Cancer Foundation (PR2018-0095), the Swedish Research Council (2015-00162), the Sjöberg Foundation, the Swedish Pain Relief Foundation, and the European Research Council (ERC-AdG-695376 and TAROX).
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T.H. is inventor on patents related to targeting DNA damage response and repair, receives royalty from PARP-inhibitor sales, and is a shareholder of Oxcia.
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Helleday, T. Polθ inhibitors unchained. Nat Cancer 2, 581–583 (2021). https://doi.org/10.1038/s43018-021-00225-5
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DOI: https://doi.org/10.1038/s43018-021-00225-5
