Talazoparib enhances resection at DSBs and renders HR-proficient cancer cells susceptible to Polθ inhibition.
Xixi LinAashish SoniRazan HessenowYanjie SunEmil MladenovMaja GuberinaMartin StuschkeGeorge IliakisPublished in: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (2024)
We propose that talazoparib promotes low-dose, CtIP/MRE11-dependent resection and increases the reliance of irradiated HR-proficient cancer cells, on Polθ-mediated alt-EJ. The combination of Polθ inhibitors with talazoparib suppresses this option and causes further radiosensitization. The results suggest that Polθ inhibition may be exploited to maximize talazoparib radiosensitization of HR-proficient tumors in the clinic.
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