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• W4366463407 abstract "Breast and ovarian tumors with pathogenic variants in BRCA1 or BRCA2 genes are more sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi) treatment than wildtype tumors. Pathogenic variants in non-BRCA1/2 homologous recombination repair genes (HRR) also concede sensitivity to PARPi treatment. RAD50 participates in the Mre11-RAD50-Nbn (MRN) complex of the HRR pathway and plays an important role in DNA repair.The objective of this study is to evaluate whether RAD50 protein deficiency modulates the PARPi response in breast cancer cell lines.T47D breast cancer cell line was modified using small interfering RNA and CRISPR/Cas9 technology, to knockout the RAD50 gene. PARPi response (niraparib, olaparib and rucaparib alone or in combination with carboplatin), in T47D and T47D-edited clones, was evaluated by cell viability, cell cycle, apoptosis and protein expression analyses.Treatment with niraparib and carboplatin exerted a synergistic effect on T47D-RAD50 deficient cells and an antagonistic effect on T47D cells parental. Cell cycle analysis demonstrated an increase in the G2/M population in cells treated with niraparib or rucaparib alone or in combination with carboplatin. T47D-RAD50 deficient cells treated with rucaparib and carboplatin exhibited twofold levels in late apoptosis, also showing differences in PARP activation. All T47D RAD50 deficient clones treated with niraparib or rucaparib combined with carboplatin, or rucaparib alone showed increased levels of H2AX phosphorylation.T47D RAD50 deficient cells treated with PARP inhibitors alone or in combination with carboplatin showed cell cycle arrest in the G2/M phase, leading to death by apoptosis. Thus, RAD50 deficiency may be a good biomarker for predicting PARPi response." @default.
• W4366463407 created "2023-04-22" @default.
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• W4366463407 date "2023-12-01" @default.
• W4366463407 modified "2023-10-05" @default.
• W4366463407 title "RAD50 Deficient in a Breast Cancer Model Predicts Sensitivity to PARP Inhibitors" @default.
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• W4366463407 doi "https://doi.org/10.2174/1568009623666230418101511" @default.
• W4366463407 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37076963" @default.
• W4366463407 hasPublicationYear "2023" @default.
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