The emerging role of exosomal circRNAs in modulating apoptotic pathways and overcoming cancer therapy resistance

Exosomal circular RNAs (circRNAs) have emerged as key regulators of tumor apoptosis, with significant implications for cancer development and treatment response. These persistent, covalently closed-loop RNAs are preferentially packed into exosomes, which are nanoscale extracellular vesicles that allow cells to communicate within the tumor microenvironment. This study investigates the molecular mechanisms underlying exosomal circRNA synthesis, selective cargo sorting, and their modulatory effects on apoptotic signaling pathways in various malignancies, including hepatocellular carcinoma, lung, gastric, pancreatic, and colorectal cancers. Exosomal circRNAs regulate apoptosis primarily through microRNA sponging, interaction with RNA-binding proteins, and the encoding of functional peptides, which influence tumor cell survival, treatment resistance, and metastatic potential. We highlight recent advances in the translational potential of exosomal circRNAs as diagnostic biomarkers and therapeutic targets for overcoming apoptosis evasion in malignancies. Targeting exosomal circRNA-mediated apoptotic networks is a promising approach to precision oncology and better clinical outcomes. This review highlights the critical need for more mechanistic and clinical investigations to utilize exosome biology in cancer therapy innovation.