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Table 2 The roles and potential applications of ecDNA in cancers

From: Small ring has big potential: insights into extrachromosomal DNA in cancer

Cancers Current advances The connection between ecDNA and clinical applications Refs.
I. Serving as potential biomarker to assess clinical outcomes
 Thyroid cancer Development of a noninvasive diagnostic tool for biopsy EcDNA is a component in liquid biopsy of thyroid cancer as a new plasma genotyping source [42]
 Cervical cancer Development of a computational diagnosis method The presence of ecDNA-viral structures is verified in cervical cancer samples [43]
 Ovarian cancer Mouse xenograft model Ciuculating DNA complements miRNAs and linear DNA for diagnosis [44]
 Non-small-cell lung cancer (NSCLC) Application in the FLAURA phase III trial Circulating tumor DNA (ctDNA) serves as primary objective to depict genetic tumor profile [45]
 Hepatocellular carcinoma (HCC) Study in biopsy and plasma samples in HCC patients ecDNA tracks real-time therapeutic responses and could overcome tumor heterogeneity [98]
 Cancers Genes on ecDNA Functions Refs.
II. Elimination of oncogenes reside on ecDNA increases drug-sensitivity
 Glioblastoma MYC, EGFR, PDGFRα, ERBB2, CDK4, MDM2 Amplification of EGFRvIII results in erlotinib resistance [48]
 Colon cancer DHFR, c-MYC Down-regulation of DHFR on ecDNA increases MTX sensitivity [57, 94, 95]
 Neuroblastoma MYCN Elimination of MYCN on ecDNA increases HU sensitivity [67]
 Cervical cancer DHFR Amplification of DHFR promote MTX resistance [96]
 Ovarian cancer MYCN, EIF5AR, CA125 Decreased levels of ecDNA-form CA125 after HU treatment [97]
 Breast cancer DHFR, HER2 Loss of HER2 residing on ecDNA has no effect on trastuzamab therapy [98, 99]
 Leukemia c-MYC Down-regulation of c-MYC promotes drug sensitivity [100]
 Oral squamous cell carcinoma MDR1 Loss of MDR1 enhances HU sensitivity [101]
III. Extracellular vesicles carrying ecDNA transfer oncogenes and trigger tumorigenesis
 Ovarian cancer Studies of EVs from cancer cells remain in the laboratory stage ecDNA can be encapsulated in EVs. EVs might have applications on clinic for tumor diagnosis, prognosis or potential treatment [19]