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The emergence of metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT) exemplifies the complex disease management for PCa. PARP inhibitors (PARPis) are being tested to treat mCRPC in tumors with defective homologous recombination repair (HRR) to address this complexity. However, increasing resistance towards PARPi in HRR-deficient patients and the low percentage of HRR-defective mCRPC patients requires the identification of new genes whose deficiency can be exploited for PARPi treatment. XRCC1 is a DNA repair protein critical in the base excision repair (BER) and single strand break repair (SSBR) pathways. We analyzed PCa patients\u2019 cohorts and found that XRCC1 expression varies widely, with many patients showing low XRCC1 expression. We created XRCC1 deficiency in PCa models to examine PARPi sensitivity. XRCC1 loss conferred hypersensitivity to PARPi by promoting the accumulation of DNA double-strand breaks, increasing cell-cycle arrest, and inducing apoptosis. We confirmed that XRCC1 expression correlated with PARPi sensitivity using a doxycycline-inducible system. Therefore, we conclude that XRCC1 expression level predicts response to PARPi, and the clinical utility of PARPi in PCa can extend to low XRCC1 expressing tumors.<\/jats:p>","DOI":"10.1093\/narcan\/zcaf015","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T10:32:19Z","timestamp":1745404339000},"source":"Crossref","is-referenced-by-count":3,"title":["PARP inhibitor response is enhanced in prostate cancer when XRCC1 expression is reduced"],"prefix":"10.1093","volume":"7","author":[{"given":"Kaveri","family":"Goel","sequence":"first","affiliation":[{"name":"Department of Pathology, Heersink School of Medicine,\u00a0The University of Alabama at Birmingham , Birmingham , AL 35294 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vani","family":"Venkatappa","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine , Houston , TX 77030 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