Table 2.
Clinical trial or experimental model on immune checkpoint inhibitor and metabolic intervention.
| Pathway | Mechanism | Drugs | Trial(Phase)/Experimental Model | Result |
|---|---|---|---|---|
| Immune checkpoint inhibitor | ||||
| PD-1 pathway | blocking PD-L1 and PD-1 interaction | Atezolizumab |
NCT02108652 (IMVigor210, phase II) NCT02302807 (IMVigor211, phase III) |
FDA-approved first-line and second-line therapy of UC |
| Avelumab | NCT01772004 (JAVELIN, phase III) | FDA-approved second-line and maintenance therapy of UC | ||
| Durvalumab | NCT01693562 (Study 1108, phase I/II) | FDA-approved second-line therapy of UC | ||
| Nivolumab |
NCT01928394 (CheckMate 032, phase I/II) NCT02387996 (CheckMate-275, phase II) |
FDA-approved second-line therapy of UC | ||
| Pembrolizumab | NCT02256436 (KEYNOTE-045, phase III) | FDA-approved first-line and second-line therapy of UC | ||
| CTLA-4 pathway | blocking CTLA-4 and CD80/86 interaction | Tremelimumab | NCT02527434 (phase II) | comparable efficacy as PD-1/PD-L1 inhibitor, but more side effects |
| Ipilimumab | - | - | ||
| Combination therapy of PD-1 and CTLA-4 pathway | blocking on PD-1 and CTLA-4 pathway | Nivolumab + Ipilimumab |
NCT01928394 (CheckMate 032, phase I/II) | higher objective response rate to nivolumab monotherapy |
| NCT03036098 (CheckMate 901, phase III) | ongoing | |||
| Metabolic intervention | ||||
| Glycolysis pathway | inhibit glycolysis via increasing deacetylase activity of SIRT6 | Ellagic acid | Cellular model | anti-tumor effect |
| Lactate transport and metabolic | inhibit SLC16A1 and SLC16A7 | AZ3965 | NCT01791595 (phase I) | ongoing |
| α-cyano-4-hydroxycinnamate | Cellular model | inhibit tumor proliferation and induce apoptosis | ||
| LDHA inhibitor | Galloflavin | Cellular model | reduce cancer cells’ growth and induce apoptosis | |
| Glutamine transport and metabolic | glutamine antagonist | 6-diazo-5-oxo-L-norleucine | Cellular model | anti-tumor effect |
| glutaminase inhibitor | CB-839 | NCT03875313 (phase I/II) | ongoing | |
CTLA-4: cytotoxic T lymphocyte-associated antigen 4; FDA: U.S Food and Drug Administration; PD-1: programmed death 1; PD-L1: programmed death ligand 1; UC: urothelial carcinoma; LDHA: lactate dehydrogenase A.