Profiling Extrachromosomal Circular DNA (ecDNA) in Cancer via Next-Generation Sequencing: A New Frontier in Tumor Evolution and Therapy Resistance

Scritto il 20/10/2026
da Sareh Bakhshandeh Bavarsad

Anticancer Agents Med Chem. 2026;26(16):1497-1516. doi: 10.2174/0118715206411197251203122339.

ABSTRACT

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.

PMID:42897892 | DOI:10.2174/0118715206411197251203122339