Circular RNAs and doxorubicin resistance in cancer: molecular mechanisms and potential treatment targets

Abstract

Doxorubicin (DOX) is a potent chemotherapeutic drug that targets Topoisomerase II in rapidly dividing tumor cells. Nonetheless, several resistance mechanisms diminish the sensitivity of cancer cells, resulting in treatment failure and disease recurrence, thereby limiting drug's efficiency. Addressing this issue entails investigating the molecular pathways responsible for DOX sensitivity or resistance and devising novel methodologies to enhance tumor cell DOX sensitivity. These mechanisms include DNA repair, cancer stem cell development, epithelialmesenchymal transition, and altered cell death. Researchers have recently found a new type of RNA molecule called circular RNAs (circRNAs), which form a closed-loop structure and change how tumors grow and invade by binding to miRNAs, controlling transcription, and interacting with proteins. Recent studies have revealed their role in mediating resistance to different anticancer agents, including DOX, targeted therapies, and immunotherapy. This review discusses diverse functions and mechanisms of circRNAs. This included drug efflux, apoptosis, interaction with the tumor microenvironment (TME), autophagy, and stopping DNA damage repair in the context of cancer drug resistance, especially DOX. Additionally, we emphasized the significance of circRNAs as novel therapeutic targets and prognostic biomarkers in the field of cancer drug resistance.