Unlocking the power of non-coding RNAs: toward real-time cancer monitoring in precision oncology

Precision oncology has transformed cancer care by tailoring treatments to individual molecular profiles, but many patients still fail to benefit from current therapies. In this context, biomarkers, particularly those measurable in non-invasive liquid biopsies, offer a promising path toward more effective and dynamic therapeutic strategies. Traditionally, circulating tumor DNA (ctDNA) has guided therapeutic decisions, but its limitations in capturing tumor complexity are becoming increasingly apparent. Conversely, non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are emerging as powerful biomarkers due to their stability in all body fluids and their dynamic regulation in response to treatment. Encapsulated in extracellular vesicles (EVs) or associated with protein/lipid complexes, circulating ncRNAs are released by both tumor and microenvironmental cells, offering a unique biological insight. This review highlights the unique potential of ncRNAs as longitudinal biomarkers for monitoring therapeutic responses, detecting recurrence, and personalizing cancer management in real time, marking the beginning of a new era in precision oncology.