Exosomal non-coding RNAs in persistence of cancer stem cells: mechanistic insights and therapeutic opportunities to mitigate risk of recurrence

Exosomal non-coding RNAs (ncRNAs) are recognized as functionally active molecules that mediate communication between the tumor microenvironment (TME) and cancer stem cells (CSCs). While individual studies have reported this crosstalk, an integrated overview of how TME-derived exosomal ncRNAs versus tumor-derived exosomal ncRNAs co-ordinately drive CSC metabolic and epigenetic plasticity to sustain stemness and therapy resistance is warranted. This review critically explores recent evidences regarding how exosomal ncRNAs released by the tumor or TME-stromal components, like cancer-associated fibroblasts, macrophages and mesenchymal stem cells, rewire CSC metabolic plasticity under different stress conditions. These exosomal ncRNAs can direct specific adaptations in CSCs that help them escape cell death and co-evolve with the TME. Additionally, emerging links between environmental or lifestyle exposures and CSC regulation via exosomal ncRNAs, an area that remains obscure yet highly relevant to cancer prevention and treatment, has been divulged. Beyond mechanistic insights, the opportunities and challenges of exploiting exosomal ncRNAs as non-invasive biomarkers and therapeutic targets has also been delineated. Current research may thereby advance the development of exosomal ncRNAs as ultra-sensitive liquid biomarkers for predicting CSC-mediated disease relapse and design therapeutic strategies to eliminate the drug resistant populations in patients to ensure good patient prognosis.