Table 1.
Drugs and targets for preventing cell plasticity
| Therapeutic intervention (single/in combination | Clinical status of drug | Clinical outcome | Indications | Ref |
|---|---|---|---|---|
| Histone deacetylases | ||||
| Vorinostat and bicalutamide | Phase II | All patients have evidence of prostate disease at the time of surgery | Localized prostate cancer | [220] |
| Vorinostat and gefitinib | Phase I/II | Patients with non-selected NSCLC tolerated the treatment well; however, the PFS did not improve | Progressive NSCLC with relapse or resistance | [221] |
| Nanatinostat | Phase I | Positive toxicological profile | Progressive solid tumors | [222] |
| Panobinostat and bicalutamide | Phase I/II | Improved progression-free survival | Castration-resistant prostate cancer (CRPC) | [223] |
| Vorinostat | Phase I | Recruiting | Melanoma generally resistant to BRAF/MEK inhibitors | [224] |
| Vorinostat and erlotinib | Phase I/II | There is no significant action in the erlotinib-resistant group | EGFR-mutant NSCLC with relapse | [225] |
| Bromodomain and extraterminal (BET) domain | ||||
| BI894999 | Phase Ia/Ib | Recruiting | Hematological disorders and progressive solid tumors | [226, 227] |
| PLX2853 | Phase Ia/IIb | Recruiting | Hematological disorders and progressive solid tumors | [227] |
| RG6146 | Phase I | Patients with diffuse large B cell lymphoma (DLBCL) have a tolerable safety profile | Hematological disorders and progressive solid tumors | [228] |
| Cyclin-dependent kinase CDK7/12 | ||||
| ICEC0942 | Preclinical | Antitumor efficacy in several cancer model organisms | ER-positive breast cancer | [229] |
| SY-1365 | Phase I | Recruiting | Progressive solid tumors | [230] |
| Histone demethylases (KDM5 and KDM6) | ||||
| YUKA1, CPI-455 (KDM5A-specific), KDOAM-25 (KDM5A-D-specific) | Preclinical | In multiple cancer models, YUKA1 inhibits drug tolerance in EGFR mutant lung cancer treated with gefitinib | NSCLC with EGFR mutation | [231–234] |
| GSK-J4 (KDM6-specific) | Preclinical | Hinders the proliferation of cells in glioblastoma | Glioblastoma | [193, 235] |
| Cell signaling mechanism | ||||
| IL-6-STAT3 signaling | ||||
| Siltuximab and docetaxel | Phase I | CRPC effectiveness when combined with docetaxel | Castration-resistant prostate cancer (CRPC) | [236, 237] |
| Notch signaling: γ-secretase inhibitor (GSI) | ||||
| RO4929097 | Phase I | Trials of RO4929097 were prematurely discontinued due to a lack of clinical benefits | Glioblastoma that is persistent or recurrent | [238] |
| MK0752 | Phase I | Weekly dosage was well tolerated, and clinical advantages were seen | Breast cancer, which is progressing | [239] |
| WNT signaling | ||||
| LGK-974 | Phase I | Initial findings point to a tolerable safety profile | Malignancies dependent on WNT | [240] |
| CGX1321 | Preclinical | Recruiting | Progressive solid tumors | [241] |
| Wnt-C59 | Preclinical | Mammary tumor progression was stopped in mice without any obvious toxicity | Adenocarcinomas of the breast | [242] |
| Anti-LRP6 | Preclinical | Delayed growth of the tumor | Colorectal cancer | [243, 244] |
| Tumor necrosis factor (TNF) signaling | ||||
| BMS345541, SC-514, and MAPK inhibitor | Preclinical | Increased effectiveness of MAPK inhibitors in melanoma (skin cancer) | Skin cancer | [245] |