Introduction: Extrachromosomal circular DNA (ecDNA) has emerged as a critical factor in cancer biology. Unlike chromosomal DNA, ecDNA exists as circular, non-centromeric molecules that can carry oncogenes, promoting tumor growth, genetic diversity, and resistance to therapy. Methods: In this review, we explored recent findings on ecDNA in human cancers, highlighting its structural characteristics, formation mechanisms, and functional roles. We examined how next-generation sequencing (NGS) technologies-such as whole-genome sequencing, Circle-Seq, and single-cell approaches-have improved the identification and characterization of ecDNA and exosomal DNA (exoDNA). Multi-omics integration was also reviewed to better understand ecDNA dynamics. Results: Studies show that ecDNA contributes to oncogene amplification, enhances chromatin accessibility, and promotes tumor heterogeneity. NGS-based techniques have enabled more precise profiling of ecDNA in various cancers. ExoDNA, released through tumor-derived exosomes, has been detected in body fluids and mirrors the genetic landscape of the originating tumor cells. Discussion: The flexible and mobile nature of ecDNA allows cancer cells to rapidly adapt and resist treatment. Its ability to form hubs and interact with enhancer regions plays a central role in altering gene expression. Targeted therapeutic strategies against ecDNA are currently under investigation and may open new avenues in personalized cancer treatment. Conclusion: EcDNA is a promising biomarker and therapeutic target in oncology. Advances in sequencing and integrative analysis provide new opportunities to understand tumor evolution and develop more effective, tailored interventions.
Bavarsad et al. (2026) studied this question.