Anti-cancer agents in medicinal chemistry · 2026
Profiling Extrachromosomal Circular DNA (ecDNA) in Cancer via Next-Generation Sequencing: A New Frontier in Tumor Evolution and Therapy Resistance.
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Bavarsad Sareh Bakhshandeh, Mohammadgholiha Narges, Hayati Mohammad Javad, Khojini Javad Yaghmoorian, Haghighi Fatemeh Sadat, Azimi Amirhossein, Gheibihayat Seyed Mohammad
Аннотация
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.
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.