The amount of ecDNA was reduced in MTX-resistant HT-29 colon cancer cells by silencing the breast and ovarian cancer susceptibility protein 1 (BRCA1) gene and the protein kinase, DNA-activated, catalytic subunit (PRKDC) gene, both of which are key players in the HR pathway and the NHEJ pathway, respectively [26, 27]. Here, PRKDC is linked to malignant colon neoplasm.