Table 1.
The drugs targeting CSCs in clinical trials.
| Signaling Pathway | Drug | Effective in preclinical studies | Clinical trials | ||
|---|---|---|---|---|---|
| Cancer | Reference | NCT no. (cancer) | Outcome | ||
| Notch | MK-0752 | Breast cancer | (14) | NCT00645333 (Breast cancer) | Not reported |
| PF-03084014 | Triple negative breast cancer | (15) | NCT01981551 (Desmoid tumors) | PR in 29%; SD in 29% | |
| Demcizumab | Non-squamous non-small cell lung cancer (NSCLC) | (16) | NCT02289898 (locally advanced solid tumors) | Placebo vs demcizumab ORR: 44.2% vs 33.1% CBR: 70.6% vs 74.3% Median PFS: 5.5 months in both arms |
|
| WNT | PRI-724 | Colorectal cancer | (17) | NCT01764477(pancreatic cancer) | SD in 40.0%; Median PFS: 2 months (range 0.7-7.7) |
| DKN-01 | Nil | NA | NCT02013154 (solid tumors) | Encouraging early efficacy signals | |
| Hedgehog | Glasdegib | Acute myeloid leukemia | (18) | NCT01546038 (acute myeloid leukemia) | CRs in 17.0% Median OS: 8.8 months |
| Vismodegib | Breast cancer | (19) | NCT00833417 (basal cell carcinoma) | ORR 48.5% in metastatic BCC group and 60.3% in the locally advanced BCC group; Median DoR: 14.8 months and 26.2 months, respectively. | |
| Hippo | Pivonedistat | Chronic myeloid leukemia | (20) | NCT01862328 (solid tumors) | CR in 3.7%; PR in 18.5%; SD in 78.6% treated at MTD; Median DoR: 5.9 months |
| JAK | Ruxolitinib | Gastric cancer | (21) | NCT01594216 (breast cancer) | Not reported |
| PI3K | BYL719 | Medulloblastoma | (22) | NCT01613950 (gastric cancer) | Not reported |
| EGFR | Bevacizumab | Melanoma | (23) | NCT01190345 (breast cancer) | Not reported |
| CXCR4 | BL-8040 Plerixafor |
Nil Colon cancer |
NA (24) |
NCT02907099 (solid tumors) NCT00512252 (acute myeloid leukemia) |
Not reported ORR 46%; median DoR 19.8 months. The median OS was 8.2 months with RFS of 9.0 months. One-year OS and RFS were 37% and 42.9%. |
| FAK | Defactinib/VS-6063 | Breast cancer | (25) | NCT04439331 (solid tumors) | Not reported |
| BCL2 | Venetoclax | Acute myeloid leukemia | (26) | NCT03466294 (acute myeloid leukemia) | Not reported |
| MDR | Dofequidar/MS-209 | Breast cancer | (27) | NCT00004886 (solid tumors) | Not reported |
| ABCG2 | Cyclosporin | NCT00983424 (breast cancer) | Not reported | ||
| EpCAM | Catumaxomab | Pancreatic carcinoma | (28) | NCT00836654 (malignant ascites) | Increased OS |
BCC, basal cell carcinoma; CBR, clinical benefit rate; CR, complete response; DLL, Delta-like ligand; DoR, duration of response; MTD, maximum tolerated dose; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; PFA, prostate-specific antigen; SD, stable disease.