Table 2.
Clinical trials of circRNAs related signaling pathways in CRC.
| Drug | Signaling pathway | Therapeutic targets | Phase | Reference/NCT number | Identified circRNAs |
|---|---|---|---|---|---|
| Encorafenib | MAPK | BRAF inhibitor | Phase I | (118) | Circ_0131663 (70) Circ-ITGA7 (71) CIRS-7 (72) |
| Vemurafenib | MAPK | BRAF inhibitor | Phase II | NCT00405587 | |
| Trametinib + panitumumab | MAPK | MEK inhibitor and anti-EGFR antibody | Phase II | NCT02399943 | |
| Dabrafenib + trametinib | MAPK | BRAF inhibitor and MEK inhibitor | Phase I/II | (122) | |
| Dabrafenib + panitumumab | MAPK | BRAF inhibitor and anti-EGFR antibody | Phase I | NCT01750918 | |
| Vemurafenib + cetuximab/panitumumab | MAPK | BRAF inhibitor and anti-EGFR antibody | Phase I/Phase II | (121) | |
| Encorafenib + cetuximab | MAPK | BRAF inhibitor and anti-EGFR antibody | Phase III | NCT02928224 | |
| Encorafenib + cetuximab + binimetinib | MAPK | BRAF inhibitor, anti-EGFR antibody with MEK inhibitor | Phase III | NCT02928224 | |
| Dabrafenib + trametinib + panitumumab | MAPK | BRAF inhibitor and MEK inhibitor with anti-EGFR antibody | Phase I | NCT01750918 | |
| PX-866 + cetuximab | PI3K/AKT | PI3K pan-inhibitor and anti-EGFR antibody | Phase II | (125) | Circ_0008285 (79) Circ-IL4R (80) |
| BKM120 (buparlisib) | PI3K/AKT | PI3K pan-inhibitor | Phase I/Phase II | (126)/NCT01833169 | |
| BKM120 + irinotecan/docetaxel | PI3K/AKT | PI3K pan-inhibitor | Phase I/Phase I | NCT01304602/NCT01540253 | |
| BKM120 + panitumumab/paclitaxel/everolimus | PI3K/AKT | PI3K pan-inhibitor and anti-EGFR antibody/mTOR inhibitor/mTOR inhibitor | Phase I/II/Phase III/Phase I | NCT01591421/NCT04338399/NCT01470209 | |
| GDC-0941 | PI3K/AKT | PI3K pan-inhibitor | Phase I | NCT00876109 | |
| GDC-0941 + erlotinib | PI3K/AKT | PI3K pan-inhibitor and anti-EGFR antibody | Phase I | NCT00975182 | |
| MEN1611 | PI3K/AKT | PI3K Selective-inhibitor | Phase I/Ib | NCT04495621 | |
| MEN1611 + cetuximab | PI3K/AKT | PI3K Selective-inhibitor and anti-EGFR antibody | Phase I | NCT04495621 | |
| KRX-0401 | PI3K/AKT | AKT inhibitor | Phase I | (127) | |
| MK-2206 | PI3K/AKT | AKT inhibitor | Phase II | NCT01802320 | |
| GDC-0068 | PI3K/AKT | AKT inhibitor | Phase I | NCT01090960 | |
| PF-05212384 | PI3K/AKT | PI3K/mTOR inhibitor | Phase I | (128) | |
| BEZ235 | PI3K/AKT | PI3K/mTOR inhibitor | Phase I | (129) | |
| GDC-0980 | PI3K/AKT | PI3K/mTOR inhibitor | Phase I | NCT00854152 | |
| DS-7423 | PI3K/AKT | PI3K/mTOR inhibitor | Phase I | NCT01364844 | |
| PKI-587 | PI3K/AKT | PI3K/mTOR inhibitor | Phase I | NCT00940498 | |
| XL-765 | PI3K/AKT | PI3K/mTOR inhibitor | Phase I | NCT00485719 | |
| XL-765 + erlotinib | PI3K/AKT | PI3K/mTOR inhibitor and anti-EGFR antibody | Phase I | NCT00777699 | |
| Temsirolimus + irinotecan/cetuximab | PI3K/AKT | mTOR inhibitor/anti-EGFR antibody | Phase II/Phase I | NCT00827684/NCT00593060 | |
| Everolimus | PI3K/AKT | mTOR inhibitor | Phase II | NCT00419159/NCT01387880/NCT00337545 | |
| Everolimus + BEZ235 | PI3K/AKT | mTOR inhibitor + PI3K/mTOR inhibitor | Phase I/II | NCT01508104 | |
| AZD2014 + paclitaxel | PI3K/AKT | mTORC1/mTORC2 inhibitor | Phase I | NCT02193633 | |
| Encorafenib + cetuximab + alpelisib | MAPK and PI3K/AKT | BRAF inhibitor, anti-EGFR antibody with PI3K inhibitor | Phase I/IIb | (123) | Circ_0131663 (70) Circ-ITGA7 (71) CIRS-7 (72) Circ_0008285 (79) Circ-IL4R (80) |
| BKM120 + binimetinib | PI3K/AKT and MAPK | PI3K pan-inhibitor and MEK inhibitor | Phase Ib | NCT01363232 | |
| BYL719 + LGX818 + cetuximab | PI3K/AKT and MAPK | PI3K Selective-inhibitor, BRAF inhibitor with anti-EGFR antibody | Phase I | NCT01719380 | |
| MK-2206 + AZD6244 | PI3K/AKT and MAPK | AKT inhibitor and MEK inhibitor | Phase II | NCT01333475 | |
| PF-04691502 + PD-0325901 | PI3K/AKT and MAPK | PI3K/mTOR inhibitor and MEK inhibitor | Phase I | (130) | |
| BEZ235 + binimetinib | PI3K/AKT and MAPK | PI3K/mTOR inhibitor and MEK inhibitor | Phase I | NCT01337765 | |
| XL147 + pimasertib/erlotinib | PI3K/AKT and MAPK | PI3K/mTOR inhibitor and MEK inhibitor/anti-EGFR antibody | Phase I | NCT01357330/NCT00692640 | |
| Bevacizumab | VEGF | anti-VEGFA antibody | FDA approved | (131) | Circ_001971 (31) Circ_0056618 (86) |
| Regorafenib | VEGF | anti-VEGFR antibody | FDA approved | (131) | |
| Ramucirumab | VEGF | anti-VEGFR antibody | FDA approved | (131) | |
| Ziv-aflibercept | VEGF | anti-VEGF antibody | FDA approved | (131) | |
| Napabucasin | JAK/STAT | STAT3 inhibitor | Phase III | (132) | Circ_0004104 (19) Circ_0000372 (28) |
| Napabucasin + bevacizumab + FOLFIRI (5‐FU, leucovorin, and irinotecan) | JAK/STAT and VEGF | STAT3 inhibitor and anti-VEGFA antibody | Phase I | NCT02641873 | Circ_001971 (31) Circ_0056618 (86) Circ_0004104 (19) Circ_0000372 (28) |
| Ruxolitinib + regorafenib | JAK/STAT and VEGF | JAK1/2 inhibitor and anti-VEGFR antibody | Phase II | NCT02119676 | |
| OMP-52M51 | Notch | anti-Notch1 antibody | Phase I | (133) | Circ-NSD2 (27) Circ-APLP2 (96) |
| RO4929097 | Notch | Gamma secretase inhibitor | Phase I | NCT01116687 | |
| OMP131R10 | WNT/β-catenin | Wnt-receptor complex inhibitor | Phase I | NCTO2482441 | Circ_0068464 (105) Circ_0082182 (106) Circ_0026628 (107) Circ_0000523 (109) Circ-MTO1 (109) Circ-PRKDC (111) |
| PRI-724 | WNT/β-catenin | Wnt-receptor complex inhibitor | Phase I/II | NCT01764477 | |
| Foxy 5 | WNT/β-catenin | Wnt-receptor complex inhibitor | Phase I/ | NCTO2655952 | |
| LGK974 | WNT/β-catenin | Wnt-receptor complex inhibitor | Phase I/II | NCTO2278133 | |
| ETC-159 | WNT/β-catenin | Wnt-receptor complex inhibitor | Phase I | NCTO2521844 |