Table 2.
Summary of studies using liquid biopsy to predict or monitor response to treatment in patients with ovarian cancer (n≥10).
| Tumor subtype and stage | n | Specimen | Laboratory method | Genetic marker | Treatment | Outcome or Clinical application | Ref. |
|---|---|---|---|---|---|---|---|
| ctDNA or cfDNA | |||||||
| Mutations | |||||||
| Stage I–IV EOC | 137 | Plasma | DNA sequencing, PCR | TP53 | PBC | Response monitoring | (89) |
| Relapsed HGSOC | 40 | Plasma | Microfluidic digital PCR | TP53 | Chemotherapy (PBC or not) | Response monitoring | (90) |
| PSR HGSOC | 18 | Plasma | NGS | TP53 | PARP inhibitor (rucaparib) | Response monitoring | (91) |
| Stage II–IV HGSOC | 102 | Plasma | ddPCR | TP53 | Platinum–taxane | Response monitoring | (92) |
| Stage I–IV HGSOC | 30 | Plasma | NGS | BRCA1/BRCA2 reversion | PBC and PARP inhibitor | Treatment resistance | (93) |
| Stage III–IV HGSOC | 19 | Plasma | NGS | BRCA1/BRCA2 reversion | PARP inhibitor | Resistance | (94) |
| Stage I–IV ovarian cancer | 121 | Plasma | NGS | Pathogenic germline or somatic BRCA1/BRCA2 | PARP inhibitor | Sensitivity/response | (95) |
| HGSOC | 97 | Plasma | NGS | BRCA1/BRCA2 reversion | PARP inhibitor (rucaparib) | Primary and acquired resistance | (96) |
| Stage III–IV HGSOC | 38 | Serum | Tagged-amplicon deep sequencing | Mutations in TP53, PTEN, BRAF, KRAS, EGFR, and PIK3CA | PBC | Response monitoring | (30) |
| Stage I–IV ovarian clear cell carcinoma | 29 | Plasma | ddPCR | Mutations in KRAS and PIK3CA | PBC | Response monitoring | (97) |
| Stage III–IV HGSOC | 14 | Plasma | NGS/Ion Torrent panel | Ion Torrent panel genes | Neoadjuvant PBC | Response monitoring | (98) |
| Methylation | |||||||
| Stage I–IV EOC | 43 | Serum | Reduced representation bisulfite sequencing | COL23A1, C2CD4D, and WNT6 | PBC | Response monitoring | (25) |
| Stage I–IV HGSOC | 50 | Plasma | High-resolution melting analysis | ESR1 promoter | PBC | Treatment resistance | (99) |
| Platinum-resistant BRCA-mutated ovarian cancer | 32 | Plasma | Methylation-specific ddPCR | HOXA9 promoter | PARP inhibitor (veliparib) | Resistance | (100) |
| Stage I–IV recurrent ovarian cancer | 126 | Plasma | Methylation-specific ddPCR | HOXA9 promoter | Chemotherapy followed by maintenance therapy with PARP inhibitors or bevacizumab | Resistance | (101) |
| Other | |||||||
| Stage II–IV HGSOC | 12 | Plasma | NGS | ERBB2 amplification | PBC ± trastuzumab | Response monitoring | (102) |
| Stage I–IV ovarian cancer | 11 | Serum | RT-PCR | ctDNA level | Chemotherapy or PARP inhibitor |
Increase in ctDNA levels after the first treatment cycle is associated with response | (103) |
| CTCs | |||||||
| Stage I–IV ovarian cancer | 143 | Plasma | Immunomagnetic CTC enrichment, multiplex RT-PCR | ERCC1+ CTCs | PBC | Treatment resistance | (104) |
| Stage I–IV ovarian cancer | 65 | Plasma | AdnaTest Ovarian Cancer, multiplex RT-PCR | ERCC1+ CTCs | PBC | Treatment resistance | (105) |
| Stage I–IV ovarian cancer | 54 | Serum | Nanoroughened microfluidic-based enrichment | EpCAM+, DAPI+, CD45– | PBC | Treatment resistance | (106) |
| Stage I–IV EOC | 160 | Serum | Immunomagnetic bead screening with multiplex RT-PCR | MUC1+ CTCs | PBC | Treatment resistance | (43) |
| Exosomes | |||||||
| Stage I–IV EOC | 78 | Plasma | Nanoparticle tracking analysis, ELISA | Exosomal HLA-G | PBC | Treatment resistance | (45) |
cfDNA, cell-free DNA; ctDNA, circulating tumor DNA; CTCs, circulating tumor cells; ddPCR, droplet digital PCR; ELISA, enzyme-linked immunosorbent assay; EMT, epithelial-to-mesenchymal transition; EOC, epithelial ovarian carcinoma; HGSOC, high-grade serous ovarian cancer; IHC, immunohistochemistry; NGS, next-generation sequencing; NR, not reported; PBC, platinum-based chemotherapy; PCR, polymerase chain reaction; RT-PCR, reverse-transcriptase PCR.