The Role of ecDNA in Tumor Heterogeneity and Evolution

Extrachromosomal DNA (ecDNA) has emerged as a critical driver of tumor heterogeneity and evolution in various cancers. Unlike chromosomal DNA, ecDNA exists outside the standard genome architecture and can carry oncogenes and regulatory elements, enabling their high-level and dynamic expression. This non-Mendelian mode of inheritance allows for rapid genetic diversification, contributing to intratumoral heterogeneity and therapeutic resistance. ecDNA can amplify oncogenic signals and adapt to selective pressures, fostering clonal evolution and promoting aggressive tumor phenotypes. Its uneven segregation during cell division further enhances genomic plasticity, complicating treatment strategies. Recent advances in sequencing and imaging technologies have improved our understanding of ecDNA’s structure, function, and impact on cancer progression. Targeting ecDNA-driven mechanisms represents a promising frontier for precision oncology. This abstract highlights the pivotal role of ecDNA in shaping tumor diversity and evolutionary trajectories, underscoring its potential as a therapeutic target and biomarker.