Table 2.
CAF targeting strategies in cancers and related clinical trials
| Target | Drugs/agents | Cancer models | Mechanism of action | Phase | Trail No. |
| CAF depletion | |||||
| FAP | FAP antibody (Sibrotuzumab) | Lung cancer | Depletion FAP+ CAFs | Phase I | NCT02209727 |
| Talabostat (PT-100) | Multiple cancer types | Inhibits FAP enzymatic activity | Phase I-II |
NCT00303940, NCT00086203, NCT00083252, NCT00083239, NCT00080080 |
|
| CAF activation blocking | |||||
| Hedgehog | IPI-926 (saridegib) and GDC0049 (vismodegib) |
Pancreatic Cancer | Reduced CAF activation | Phase I-II |
NCT01130142, NCT01195415 |
| LDE225 (sonidegib) | Multiple cancer types | Inhibits Hedgehog signaling through SMO inhibition |
Phase I-II |
NCT02027376, NCT02195973, NCT02138929, NCT01487785, NCT01327053, NCT01708174, NCT01350115, NCT00961896 |
|
| CXCR4 | Plerixafor | PDAC, Ovarian and Colorectal Cancer |
Inhibit CXCL12 production, restore antitumoral immunity | Phase I |
NCT02179970 |
| Children Cancer, Solid Tumor | Phase II |
NCT01225419 |
|||
| BL-8040 | PDAC | Phase II | NCT02826486 | ||
| IL-6 receptor | Tocilizumab | Pancreatic Carcinoma | Phase II | NCT02767557 | |
| FGFR | JNJ-42756493 (erdafitinib) | Lymphoma, Adenocarcinoma, etc. | Prevents CAF activation |
Phase I | NCT01962532, NCT01703481, |
| Multiple cancer types | Phase II | NCT02699606 | |||
| Hepatocellular Carcinoma | Phase I-II | NCT02421185 | |||
| CAF Normalization | |||||
| IL-1 receptor | Anakinra | PDAC | CAF normalization | Phase I | NCT02021422 |
| Vitamin A metabolism |
ATRA | PDAC, Nephroblastoma | Normalize stellate cells | Phase I-II | NCT03307148, NCT00001509 |
| VDR | Calcipotriol | Breast Cancer, | CAF normalization | Phase I | NCT03596073 |
| Paricalcitol | Multiple cancer types | CAF normalization and improved chemotherapeutic efficacy | Phase I-II |
NCT00637897, NCT03520790, NCT03883919, NCT03415854 |
|
| ECM remodeling | |||||
| Angiotensin receptor | Losartan | Breast cancer, Pancreatic cancers | Reduces hyaluronan production by CAFs | Phase III | NCT04106856, NCT03900793, NCT01805453 |
PDAC: Pancreatic ductal adenocarcinoma; CAF: cancer-associated fibroblasts.