Multi-omics Characterization of Acquired Olaparib Resistance in BRCA1 and BRCA2 Mutant Breast Cancer Cell Lines.

ABSTRACT: Poly (ADP-ribose) polymerase inhibitors (PARPi) are widely used as targeted therapies against breast cancers with BRCA mutations. However, the development of resistance to PARPi poses a significant challenge for long-term efficacy of these therapies, warranting further understanding of mechanisms of PARPi resistance. Here, we generated and characterized Olaparib resistance in BRCA1/2 mutant breast cancer cell lines MDAMB436 and HCC1428 using a systems-level multi-omics approach, including transcriptome, proteome, phosphoproteome, and ADP-ribosylation analysis. Our analyses revealed that resistance development strongly correlated with protein expression changes, while modest effects on phosphorylation- and ADP-ribosylation-dependent signaling pathways were observed. We found that BRCA1 expr

SUBMITTER: Anagho-Mattanovich HA 

PROVIDER: S-EPMC12355081 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature