miRNAs as Theragnostic Markers for PARP Inhibitor Resistance in Breast Cancer: A Systematic Review.

This systematic review aims to evaluate the potential of mi-croRNAs (miRNAs) as theragnostic biomarkers for predicting resistance to PARP inhibitors in Breast Cancer (BC), highlighting their potential for personalized treatment strategies. Following PRISMA guidelines, we conducted a search in Scopus, EMBASE, Pub-Med, and Web of Science to identify studies on miRNAs as biomarkers for predicting PARP inhibitor response in BC. Articles were selected based on inclusion and exclusion criteria, focusing on in vitro and in vivo studies, with quality assessed using the SYRCLE tool and a customized checklist. Seventeen studies were included, identifying 15 miRNAs with different expression patterns. Two main types of miRNA interactions with PARP inhibitors were observed: syn-ergistic and antagonistic effects, mediated through signaling pathway regulation and induc-tion of a BRCAness phenotype in DNA repair mechanisms. The dual role of miRNAs in modulating PARP inhibitor response in BC is evi-dent. Several miRNAs, such as miR-451, miR-199a-3p, and miR-182, enhance PARP inhib-itor efficacy by targeting pathways like PI3K, BRCA1, and C/EBPβ. On the other hand, miR-181a and miR-214-5p contribute to resistance by upregulating STING and downregu-lating RAD51, respectively. These findings emphasize the complex role of miRNAs in ther-apy, highlighting their potential as both biomarkers and therapeutic targets in overcoming resistance. miRNAs are crucial in BC treatment with PARP inhibitors. Further clinical studies are needed to validate their roles and develop miRNA-based strategies to overcome PARP inhibitor resistance.