miRNA-dependent resistance mechanisms to anti-hormonal therapies in estrogen receptor-positive breast cancer patients.

Abstract

The estrogen receptor (ERα) is expressed in 70%-80% of breast cancers and is a target of endocrine therapy. However, resistance to endocrine therapy poses a significant clinical challenge. MicroRNAs (miRNAs) have emerged as critical players in oncogenesis and as modulators of therapy response. This review provides an overview of miRNAs that modulate anti-hormonal drug responses. We identified 56 miRNAs associated with resistance to endocrine therapy. These miRNAs had a total of 40 proven target genes that were grouped based on their function under currently known resistance mechanisms, including ER modulation, signaling pathway activation, cell-cycle modulation, and other mechanisms. For a limited number of miRNA-target gene interactions, the relevance of the identified target gene(s) was confirmed by copy or rescue of the miRNA-induced phenotype. Overall, this review highlights critical roles of miRNAs as crucial mediators of resistance to anti-hormonal therapy. The identified miRNA-target gene interactions can serve as a foundation for future functional studies exploring the potential of selected miRNAs in overcoming drug resistance, which might improve outcomes for breast cancer patients.