Table 1.
Summary of functions of eccDNAs related to cancer
| Type of cancer | Genes | Drugs/Treatment | Biogenesis | Function | References |
|---|---|---|---|---|---|
| Pancancer (17 different cancer types) | EGFR | Erlotinib | Rearrangement | Contributes to intratumoral heterogeneity via the reintegration of EGFRvIII-containing eccDNA elements and by promoting the transcription of EGFR; additional rearrangements and heterogeneity after erlotinib withdrawal. | [65] |
| Pancancer (17 different cancer types) | MYC | NA | Rearrangement | Contributes to intratumoral heterogeneity by promoting the transcription of MYC. | [65] |
| Pancancer (prostate cancer, colon cancer, glioblastoma) | EGFR, MYC, CDK4 and MDM2 | NA | NA | Promotes the expression of oncogenes (EGFR, MYC, CDK4, and MDM2) encoded on eccDNA by influencing the chromatin organization. | [7] |
| Glioblastoma | EGFR | Irradiation | NA | Cells with amplified EGFR on eccDNA exhibit stronger invasive properties and radiation resistance. | [72] |
| Glioblastoma | MET | Capmatinib | NA | Amplified MET on eccDNA drives early tumor formation, and the elimination of eccDNA increases the survival benefit. | [8] |
| Glioblastoma | MYC | NA | NA | EccDNA harboring MYC amplification contributes to recurrent tumors. | [8] |
| Glioblastoma | EGFR | Dacomitinib | NA | EccDNA harboring EGFRvIII mutation amplification drives recurrent tumors upon treatment with dacomitinib. | [8] |
| Glioblastoma | EGFRvIII | Temozolomide with adjuvant radiation | NA | EccDNA containing EGFRvIII provides cells with growth advantages. | [73] |
| Glioblastoma | MDM2 | Erlotinib | NA | The amplification of MDM2 on eccDNA promotes erlotinib resistance. | [70] |
| Neuroblastoma | MYCN | NA | Involves neo-topologically associated domains | The hijacking of enhancers and insulators drives the expression of MYC on eccDNA. | [40] |
| Neuroblastoma | MYCN | NA | DNA repair or replication-associated mechanisms | Drives oncogenic genome remodeling and the expression of oncogenes. | [6] |
| Neuroblastoma | MYCN | Hydroxyurea | NA | The elimination of amplified MYCN on eccDNAs increases the sensitivity to hydroxyurea. | [74] |
| Cervical cancer | DHFR | Methotrexate | Chromothripsis, BFB | Adaptation to increased selection pressure is induced by methotrexate by increasing the DHFR gene copies in eccDNA, which promotes DHFR expression. | [43] |
| Cervical cancer | DHFR | Methotrexate | BFB | The amplification of DHFR located on eccDNA promotes resistance to methotrexate. | [75] |
| Breast Cancer | DHFR | Methotrexate | NA | Irradiation induces methotrexate resistance due to eccDNA with amplified DHFR. | [76] |
| Oral squamous cell carcinoma | MDR1 | Hydroxyurea | NA | Loss of MDR1-carrying eccDNA induced by hydroxyurea increases drug sensitivity. | [77] |
| Colon cancer | DHFR | Methotrexate | NA | The elimination of DHFR-containing eccDNA promotes sensitivity to methotrexate and inhibits proliferation. | [78, 79] |
| Colorectal cancer | Not define | NA | Chromothripsis, a process of multistep evolution that drives eccDNA formation | eccDNA may drive cancer progression. | [80] |
| Leukemia | MYC | Hydroxyurea | NA | Hydroxyurea inhibits tumorigenicity by eliminating amplified MYC on eccDNAs. | [81] |
| Leukemia | c-Myc | Hydroxyurea and retinoic acid | NA | Hydroxyurea inhibits tumorigenicity by eliminating c-Myc-bearing eccDNAs. | [82] |
| Undefined | microRNA | NA | NA | Expresses functional small regulatory RNA. | [64] |
NA Not available