Extrachromosomal DNA (ecDNA) and Clinical Implications in Cancer

The extrachromosomal DNA (ecDNA) has recently been defined as a crucial contributor to oncogenesis due to its acentric, circular nature and ability to amplify tumor-promoting genes divorced of chromosomal organization. ecDNA provides oncogenes with privileged access to transcriptional machinery, providing the capacity to respond dynamically to environmental and therapeutic stress. It ensures the genetic instability and adaptation of tumors via mechanisms, including uneven mitotic segregation and re-introduction into chromosomes. New technological innovations in recent years, such as the use of Circle-Seq, single-cell, and live-cell imaging, have revolutionized the methodology of ecDNA detection and structural understanding, revealing its ubiquity in tumor types and participation in adaptive resistance to drugs. ecDNA is associated clinically with negative prognosis, poor response to treatment, and aggressive tumor behavior. It has a prognostic and diagnostic marker potential as it has been detected in liquid and pre-diagnostic samples, respectively. Although the standardization of detection and clinical application is weaker than it should be, ecDNA has the potential to transform precision oncology. The production of ecDNA-specific treatment, such as gene editing, pharmacological destabilization, or induction of micronuclei, together with ecDNA tracking in real time, will serve as an innovative opportunity to overcome resistance and personalize therapy. The chapter will give a detailed account of the complex functions of ecDNA in cancer biology and how it contributes to tumor heterogeneity, accelerated clonal evolution, immune escape, and acquired resistance to therapeutic agents.