Exosomal circRNAs in cancer: Implications for therapy resistance and biomarkers

Despite the advances in cancer treatment in recent years, the development of resistance to cancer therapy remains the biggest hurdle towards curative cancer treatments. Therefore, investigating the molecular mechanisms underlying cancer therapy resistance is of paramount clinical importance. Circular RNAs (circRNAs), novel members of the noncoding RNA family, are endogenous biomolecules in eukaryotes characterized by a covalently closed loop structure with multiple biological functions. Significantly, circRNAs are abundant and stable in exosomes and can be packaged, secreted and transferred to targeted tumour cells, thereby modulating diverse hallmarks of cancer behaviours, such as proliferation, migration, and immune escape. Notably, a great number of exosomal circRNAs are abnormally expressed during cancer treatment and can mediate cancer therapy resistance through complex mechanisms; therefore, targeting exosomal circRNAs is a promising therapeutic method to reverse therapy resistance. This review aimed to elucidate the mechanisms underlying exosomal circRNAs controlling the resistance of cancer to common therapies, such as chemotherapy, targeted therapy, immunotherapy and radiotherapy, and we also discussed the therapeutic potential of exosomal circRNAs as clinical biomarkers and novel targets in cancer clinical management. We also discussed the prospects and challenges of targeting exosomal circRNAs as a novel therapeutic strategy for reversing cancer therapy resistance.