Table 2 |.
Actionable therapeutic targets in genetic cholangiopathies
| Disease | Target | Agent | Refs |
|---|---|---|---|
| PLD | Somatostatin receptors (inhibitor) | Octreotide | 108,135 |
| Lanreotide | 62,63 | ||
| Pasireotide | 108 | ||
| AC5 (inhibitor) | SQ22,536 | 104 | |
| VEGFR2 (inhibitor) | SU5416 | 113,114 | |
| BRAF | Sorafenib | 107 | |
| Intracellular calcium and toxic bile acid removal | UDCA | 110 | |
| pmTOR | Rapamycin | 115 | |
| CHF/CD | Somatostatin receptors (inhibitor) | Pasireotide | 108 |
| Octreotide | 108,135 | ||
| Intracellular calcium and toxic bile acid removal | UDCA | 111 | |
| Matrix metalloproteases | Marimastat | 95 | |
| PPARγ (agonist) | Pioglitazione | 144 | |
| Telmisartan | 143,144 | ||
| Macrophages (depletion) | Clodronate | 124 | |
| CXCR3 expressed by macrophages | AMG-487 | 136 | |
| CFLD | PPARγ (agonist) | Pioglitazione | 177 |
| Rosiglitazone | 177 | ||
| CFTR function (correctors and potentiators) | Ivacaftor, lumacaftor and tezacaftor | 162,163 | |
| Src tyrosine kinase family (inhibitor) | PP2 | 164,170 |
In polycystic liver disease (PLD), octreotide, lanreotide and pasireotide are currently under evaluation in phase II–III clinical trials (octreotide in , lanreotide in and pasireotide in ). In cystic fibrosis, ivacaftor and the combinations of ivacaftor plus lumacaftor and ivacaftor plus tezacaftor are currently in use by patients with specific mutations. However, no data are available about their effect on cystic fibrosis-related liver disease (CFLD). AC5, adenylyl cyclase 5; CD, Caroli disease; CFTR, cystic fibrosis transmembrane conductance regulator; CHF, congenital hepatic fibrosis; CXCR3, CXC-chemokine receptor 3; pmTOR, phosphorylated mechanistic target of rapamycin; PPARγ, peroxisome proliferator activated receptor-γ; UDCA, ursodeoxycholic acid; VEGFR, vascular endothelial growth factor receptor.