Table 1.
Senescence-targeting therapies in clinical trials.
| Senescence Inducer | ||||||
|---|---|---|---|---|---|---|
| Category | Compound | Regimens | Phase | Population | Results | Study Number |
| CDK4/6 Inhibitor | Palbociclib (PD0332991) | Singular treatment | II | 23 patients with advanced HCC | OS: 40 (24–96) wk, 11/23 (47.83%) with severe side effects | NCT01356628 |
| Abemaciclib | Combined with nivolumab | II | 7 patients with inoperable HCC | 1/7 (14.3% ORR), PFS: 2.1 (1.6 to 5.6) mon, OS: 7.9 (2.6 to 22.7) mon, 3/7 (42.86%) severe side effects | NCT03781960 | |
| Ribociclib (LEE011) | Combined with chemoembolization | Ib/II | 5 patients with advanced HCC | 1/5 (20.00%) severe side effects | NCT02524119 | |
| SHR6390 | Combined with anti-PD-1 Inhibitor SHR-1210 | Ib/II | 41 advanced colorectal cancer, non-small-cell lung cancer and HCC | Ongoing | NCT03601598 | |
| VEGFR-2 tyrosine kinase inhibitor | AZD2171 (Cediranib maleate) | Singular treatment | II | 17 patients with locally advanced unresectable or metastatic HCC | OS: 11.7 (7.5 to 13.6) mon, 5/17 (29.41%) severe side effects | NCT00427973 |
| Senescence eliminator | ||||||
| Senolytics | Navitoclax | Combined with Sorafenib (Nexavar) | I | 44 patients with relapsed or refractory solid organ tumors including HCC | Ongoing | NCT02143401 |
| Dasatinib (BMS-354825) | Singular treatment | I | 80 patients with unresectable or metastatic solid tumors including HCC | Completed | NCT00608361 | |
| Dasatinib (BMS-354825) | Singular treatment | II | 25 patients with unresectable advanced HCC | PFS: 3.7 (1.8 to 6.4) mon, OS: 7.5 (2.9 to 13.6) mon, 13/25 (52.00%) serious side effects | NCT00459108 | |
| mTOR inhibitor | Temsirolimus | Combined with Sorafenib | I/II | Advanced HCC | Cancelled | NCT01335074 |
| Combined with pegylated liposomal doxorubicin (Doxil®) | II | Advanced HCC | Cancelled | NCT01281943 | ||
| ABI-009 | Combined with anti-PD1 inhibitor nivolumab | I/II | 26 patients with advanced sarcoma and certain cancers including HCC (with genetic mutations sensitive to mTOR inhibitors) | 4/26 (15%) serious side effects | NCT03190174 | |
| Anti-DPP4 inhibitor | Sitagliptin | Singular treatment before HCC resection | I | 14 HCC patients undergoing liver resection | No severe adverse event | NCT02650427 |