SLX1 Inhibition Enhances Olaparib Sensitivity by Impairing Homologous Recombination Repair in Breast Cancer.

ABSTRACT: While PARP inhibitors like Olaparib are effective against BRCA1-deficient breast cancers, their efficacy in BRCA1-proficient tumors depends on the functional status of homologous recombination (HR) repair. Here, we identify the structure-specific endonuclease SLX1 as a key regulator of HR and a determinant of Olaparib sensitivity in BRCA1-intact breast cancer. SLX1 is frequently upregulated in breast cancer and associated with poor prognosis. Functional studies revealed that SLX1 promotes RAD51-mediated HR repair of DNA double-strand breaks. Consequently, SLX1 depletion reduces HR efficiency, increases chromosomal instability, and sensitizes breast-proficient breast cancer cells to DNA-damaging agents, including camptothecin, ionizing radiation, and Olaparib. In contrast, SLX1 overexpressi

SUBMITTER: Kim JY 

PROVIDER: S-EPMC12692287 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature