Table 2 The roles and potential applications of ecDNA in cancers

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]

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]