Insight on ecDNA-mediated tumorigenesis and drug resistance

Abstract

Extrachromosomal DNAs (ecDNAs) are a pervasive feature found in cancer and contain oncogenes and their corresponding regulatory elements. Their unique structural properties allow a rapid amplification of oncogenes and alter chromatin accessibility, leading to tumorigenesis and malignant development. The uneven segregation of ecDNA during cell division enhances intercellular genetic heterogeneity, which contributes to tumor evolution that might trigger drug resistance and chemotherapy tolerance. In addition, ecDNA has the ability to integrate into or detach from chromosomal DNA, such progress results into structural alterations and genomic rearrangements within cancer cells. Recent advances in multi-omics analysis revealing the genomic and epigenetic characteristics of ecDNA are anticipated to make valuable contributions to the development of precision cancer therapy. Herein, we conclud the mechanisms of ecDNA generation and the homeostasis of its dynamic structure. In addition to the latest techniques in ecDNA research including multi-omics analysis and biochemical validation methods, we also discuss the role of ecDNA in tumor development and treatment, especially in drug resistance, and future challenges of ecDNA in cancer therapy.

Keywords

• ecDNA
• Tumor evolution
• Oncogene amplification
• Intratumoral heterogeneity
• Cancer therapy