ecDNA

Extrachromosomal DNA (ecDNA) emerges as a critical player in cancer drug resistance that promotes heterogeneity within tumors, oncogene amplification, and rapid adaptation of malignant cells. Unlike chromosomal DNA, ecDNA is circularly fragmented and extrachromosomal and lacks centromeres, enabling it to segregate unequally during mitosis. It offers selective developmental benefit based on promoting the expression of high levels of oncogenes, such as MYC, EGFR, and MDM2. Recent evidence demonstrates that ecDNA promotes tumorigenesis and tumor plasticity and can give rise to acquired resistance to targeted therapy, chemotherapeutic, and immune checkpoint inhibitors. Furthermore, ecDNA may disrupt epigenetic regulators, transcriptional machineries, and chromatin integrity to alter the topography of gene expression profiles, subsequently complicating the implications of therapeutic outcomes. Recent technological advances in single-cell sequencing and single-cell imaging have made it possible to understand the dynamics of ecDNA better, opening up new avenues in areas of biomarker discovery and precision oncology. This book chapter seeks to formulate a rich insight into the drug resistance mechanisms of ecDNA and to critically focus on the therapeutic application of ecDNA as a relevant focus of treatment in cancer.