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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Patel, K. J. et al. Mol. Cell 1, 347–357 (1998).
Venkitaraman, A. R. Cell 108, 171–182 (2002).
Helleday, T., Petermann, E., Lundin, C., Hodgson, B. & Sharma, R. A. Nat. Rev. Cancer 8, 193–204 (2008).
Bryant, H. E. et al. EMBO J. 28, 2601–2615 (2009).
Bryant, H. E. et al. Nature 434, 913–917 (2005).
Farmer, H. et al. Nature 434, 917–921 (2005).
Yousefzadeh, M. J. et al. PLoS Genet. 10, e1004654 (2014).
Zhou, J. et al. Nat. Cancer https://doi.org/10.1038/s43018-021-00203-x (2021).
Zatreanu, D. et al. Nat. Commun. https://doi.org/10.1038/10.1038/s41467-021-23463-8 (2021).
Ledermann, J. et al. N. Engl. J. Med. 366, 1382–1392 (2012).
Gelmon, K. A. et al. Lancet Oncol. 12, 852–861 (2011).
Ceccaldi, R. et al. Nature 518, 258–262 (2015).
Mateos-Gomez, P. A. et al. Nature 518, 254–257 (2015).
Bunting, S. F. et al. Cell 141, 243–254 (2010).
Toledo, L. I. et al. Cell 155, 1088–1103 (2013).
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).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
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.
Rights and permissions
About this article
Cite this article
Helleday, T. Polθ inhibitors unchained. Nat Cancer 2, 581–583 (2021). https://doi.org/10.1038/s43018-021-00225-5
Published:
Issue Date:
DOI: https://doi.org/10.1038/s43018-021-00225-5