The bench-to-bedside journey of circular RNAs in cancer: Status, challenges and future prospects

Cancer remains a major global health challenge, with its heterogeneity and complexity posing significant obstacles to accurate diagnosis and effective treatment. Therefore, it is imperative to find new biomarkers and therapeutic targets to develop more precise and effective strategies. Over the past decade, circular RNAs (circRNAs), a class of covalently closed RNA molecules, have emerged as promising candidates because of their stability, specific expression, and functional roles in cancer. Growing evidence suggests their potential clinical relevance and utility. In particular, owing to their stable presence and detectability in body fluids, circRNAs possess considerable potential to serve as diagnostic, prognostic, and predictive biomarkers. Additionally, promising advances have been made in the development of circRNA-based therapeutic strategies that involve both targeting endogenous circRNAs and delivering synthetic ones. In this review, we delineate the biogenesis, characteristics, and functional involvement of circRNAs in cancer and further summarize their potential as liquid biopsy biomarkers and for the development of circRNA-based therapeutic strategies. We also discuss challenges that must be overcome to unlock the full potential of circRNAs and address future directions.