Circular RNAs: key regulators and mechanistic insights in breast cancer drug resistance

Breast cancer is the most common malignancy in women, and pharmacotherapy is the cornerstone of multidisciplinary care. However, drug resistance severely impairs therapeutic efficacy and patient prognosis. Circular RNAs (circRNAs) have become a key focus in breast cancer chemoresistance due to their high stability and specific expression profiles. This review classifies circRNA functions according to breast cancer molecular subtypes, elucidating their regulatory mechanisms underlying drug resistance via RNA-RNA crosstalk, RNA-protein binding, and translational regulation. We systematically summarize the core signaling cascades through which circRNAs modulate downstream biological events, including drug efflux and DNA damage repair, to drive resistance, and highlight the vital function of exosomal circRNAs in propagating systemic drug resistance. We integrate existing research evidence into a comprehensive landscape of subtype-specific circRNA regulatory networks in breast cancer drug resistance.