Role of ecDNA in Cancer Metastasis and Disease Recurrence

Abstract

Extrachromosomal DNA (ecDNA) has emerged as a critical factor influencing cancer metastasis and recurrence, significantly altering clinical outcomes. This chapter elucidates the unique physical and genetic features of ecDNA, highlighting its distinct amplification mechanisms and substantial contribution to genetic heterogeneity within tumors. The presence of ecDNA notably impacts cancer cell behavior, fostering cellular phenotypes conducive to tumor progression, metastasis, and adaptability within the tumor microenvironment. Through oncogene amplification and intricate modulation of metastasis-related signaling pathways, ecDNA profoundly enhances metastatic potential. Clinical evidence underscores ecDNA’s involvement in disease recurrence by promoting therapy resistance and enabling survival of minimal residual disease, posing considerable challenges in cancer treatment. Targeting ecDNA represents a promising therapeutic strategy to mitigate metastasis and recurrence, yet significant technical hurdles remain. The chapter discusses these scientific and methodological challenges, outlines promising therapeutic approaches targeting ecDNA, and identifies future research directions essential for translating these insights into clinical practice. Understanding ecDNA’s role thus holds substantial promise for improving outcomes in metastatic and recurrent cancers.