Circular RNAs orchestrating breast cancer hallmarks: bridging tumor biology and therapy resistance

Abstract

Breast cancer (BC) remains a leading cause of cancer-related mortality among women worldwide, with treatment resistance posing a significant clinical challenge. Circular RNAs (circRNAs), a class of non-coding RNAs, have gained increasing attention as key regulators of gene expression, influencing BC pathogenesis, progression, and therapeutic response. This review explores the mechanistic insights into circRNA functions in BC, focusing on their involvement in tumor proliferation, metabolic reprogramming, epithelial-mesenchymal transition (EMT), angiogenesis, metastasis, and apoptosis. Additionally, we highlight the crosstalk between circRNAs and microRNAs, emphasizing their potential as diagnostic and prognostic biomarkers. Beyond their roles in tumor biology, circRNAs are implicated in drug resistance, modulating responses to chemotherapy, targeted therapy, and endocrine treatment. Despite their promising applications, challenges remain, including the complexity of circRNA interactions, and the development of robust preclinical models. Addressing these challenges through interdisciplinary research integrating genomics, transcriptomics, and functional studies will pave the way for circRNA-based therapeutic strategies and personalized medicine approaches in BC management.