EccDNA can significantly elevate copy numbers of EGFR, MDM2, CDK4, and BRAF in tumor cells, which implicates the regulation of the PI3K/AKT pathway, p53 pathway, and MAPK/ERK pathway.2,129,130 Moreover, eccDNA can also be regulated by several canonical signaling pathways. This evidence concerns the gene AKT1 and neoplasm.