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   10.64898/2026.06.18.733126

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   10.1101/2023.03.06.531305

4. Targeting Polθ Helicase with RP-3467: Preclinical Validation and Clinical Response in a g BRCA1 ovarian cancer patient with an acquired PARPi resistance mutation in TP53BP1

   This article has 32 authors:

   1. Ezra Y. Rosen
   2. Marie-Claude Mathieu
   3. Gino B. Ferraro
   4. Philippe Mochirian
   5. Claude Godbout
   6. Hugo Poirier
   7. Sara Fournier
   8. Danielle Henry
   9. Hyeyeon Kim
   10. Robert Papp
   11. Shou Yun Yin
   12. Marie-Eve Leclaire
   13. Robert Houle
   14. Parham Nejad
   15. Joseph D. Schonhoft
   16. Karl E. Zahn
   17. W. Cameron Black
   18. Michel Gallant
   19. Insil Kim
   20. Danielle Ulanet
   21. Paul Basciano
   22. Artur Veloso
   23. Victoria Rimkunas
   24. Timothy A. Yap
   25. Robin Guo
   26. Nicholas Mai
   27. Maria Koehler
   28. Michael Zinda
   29. Anne Roulston
   30. Michal Zimmermann
   31. Stephen J. Morris
   32. Agnel Sfeir

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     Loss of POLQ function is synthetically lethal with BRCA1 or BRCA2 deficiency, as is pharmacological inhibition of its motor (ATPase) or polymerase activity. This important manuscript validates an inhibitor of the DNA polymerase theta (POLθ) motor domain in biochemical and cell-based assays and provides evidence of its efficacy against homologous recombination-deficient tumors in preclinical and clinical settings, particularly in combination with PARP inhibitors. The experiments are rigorous, the evidence is convincing, and the results are appropriately interpreted. This work will be of considerable interest to the ovarian cancer research community.

   Reviewed by eLife

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