Tamoxifen remains a cornerstone therapy for estrogen receptor-positive (ER⁺) breast cancer; however, the emergence of drug resistance significantly limits its therapeutic success. Growing evidence has revealed that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), act as pivotal regulators of the molecular networks driving tamoxifen resistance. These “silent regulators” modulate multiple signaling pathways, including PI3K/AKT, MAPK, and estrogen receptor signaling, through mechanisms such as post-transcriptional regulation, epigenetic modification, and competitive endogenous RNA (ceRNA) interactions. Dysregulated ncRNAs can alter drug efflux, apoptosis, cell cycle progression, and epithelial–mesenchymal transition (EMT), contributing to reduced tamoxifen sensitivity and tumor recurrence. Our knowledge of BC resistance to tamoxifen will be aided by the new molecular insights into the mechanistic understanding of resistance to endocrine treatment as a whole that come from the growing functions of ncRNAs as miRNA sponges, transcriptional scaffolds, and ceRNAs, among others. The biosynthesis and molecular properties of ncRNAs, their involvement in tamoxifen resistance, and their potential use as therapeutic targets or diagnostic biomarkers are the main topics of this thorough analysis. In order to perhaps serve as a foundation for upcoming RNA-based therapies aimed at overcoming endocrine resistance in ER⁺ BC, we would also consolidate the current body of knowledge.
Jameel et al. (Sat,) studied this question.