Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities.

Exosomes can regulate the malignant progression of tumors by carrying a variety of genetic information and transmitting it to target cells. Recent studies indicate that exosomal circular RNAs (circRNAs) regulate multiple biological processes in carcinogenesis, such as tumor growth, metastasis, epithelial-mesenchymal transition, drug resistance, autophagy, metabolism, angiogenesis, and immune escape. In the tumor microenvironment (TME), exosomal circRNAs can be transferred among tumor cells, endothelial cells, cancer-associated fibroblasts, immune cells, and microbiota, affecting tumor initiation and progression. Due to the high stability and widespread presence of exosomal circRNAs, they hold promise as biomarkers for tumor diagnosis and prognosis prediction in blood and urine. In addition, designing nanoparticles targeting exosomal circRNAs and utilizing exosomal circRNAs derived from immune cells or stem cells provide new strategies for cancer therapy. In this review, we examined the crucial role of exosomal circRNAs in regulating tumor-related signaling pathways and summarized the transmission of exosomal circRNAs between various types of cells and their impact on the TME. Finally, our review highlights the potential of exosomal circRNAs as diagnostic and prognostic prediction biomarkers, as well as suggesting new strategies for clinical therapy.