Table 1.
Target | Cancer Type | Inhibitor | Result | Reference |
---|---|---|---|---|
ALDH1 | Breast | Histone deacetylase inhibitor | CD44+CD24−/low cell population was decreased and stemness markers were downregulated. | [27,28] |
NSCLC | Disulfiram | Combination of disulfiram and copper downregulated stemness-related genes. | [29] | |
When combined with diethylamino-benzaldehyde resensitized resistant cells to cisplatin. | [30] | |||
A phase II trial showed prolonged survival when disulfiram was combined with cisplatin and vinorelbine. | [31] | |||
Ovary | Solanum incanum extract | Notch1 and FoxM1 were downregulated, which resulted in increased chemotherapeutic sensitivities. | [32] | |
CD44 | Breast | Anti CD44 antibody | Nanoparticles with CD44 antibody and gemcitabine specifically targeted CD44+ cells. | [33] |
CD133 | Ovary | Anti CD133 antibody-toxin conjugate | Cellular growth was inhibited and tumor progression was suppressed in a mouse model. | [34] |
Hedgehog | Bladder | Cyclopamine | Tumor formation was suppressed via inhibition of GALNT1 that mediates SHH signaling. | [35] |
Lung | GDC-0449 | Stemness-related features were suppressed in both NSCLC and small-cell lung cancer cells. | [36] | |
KLF5 | Breast | Metformin | CSC growth was inhibited through suppression of NANOG and FGF-BP1 (downstream targets of KLF5). | [37,38] |
Notch2 and Notch3 | Various cancers Small-cell lung |
Tarextumab | Tumorigenesis and cellular growth were suppressed and chemotherapeutic efficacy was increased. | [39] |
A phase Ib trial showed good tolerability and anti-tumor effect. | [40] | |||
PI3K/AKT | Bladder | Myrtucommulone-A | Several stem cell markers were downregulated and stemness-related features were attenuated. | [41] |
Bladder | Motesanib | Survival-related genes in the PI3K/AKT pathway were decreased and cisplatin sensitivity was enhanced. | [42] | |
STAT3 | Breast | STAT3 inhibitor VII | Combination of STAT3 inhibitor and carboplatin abrogated carboplatin-induced ALDH+ cell enrichment. | [15] |
Colon | Napabucasin | c-Myc, Nanog and Sox2, were downregulated, which attenuated metastasis in a mouse model. | [43] | |
Napabucasin showed prolonged survival in phosphorylated STAT3 positive patients. | [44] | |||
Pancreas | Napabucasin | Cancer relapse and metastasis were blocked in mice. | [43] | |
NSCLC | OPB-51602 | A phase I trial suggested that NSCLC patients were likely to obtain better response. | [45] | |
Wnt/β-catenin | Breast | Pyrvinium pamoate | CD44+CD24−/low and ALDH+ cells were suppressed by downregulating NANOG, OCT4, and SOX2. | [46] |
Breast | Resveratol | Resveratol, which suppressed Wnt/β-catenin pathway, inhibited CSCs and induced autophagy. | [47] | |
Ovary | Imatinib | CSC activity was suppressed when combined with platinum chemotherapy. | [48] | |
Phase II clinical trials had only a modest impact on the prognosis of ovarian cancer patients. | [49,50] | |||
YAP1 | Bladder | Verteporfin | Combination of YAP1 and COX2 inhibitors with chemotherapy attenuated CSC properties and enhanced chemotherapy response. | [21] |
NSCLC Bladder |
Verteporfin | Verteporfin attenuated the resistance to EGFR inhibitors. | [21,51,52] |
NSCLC: non-small cell lung carcinoma; SHH: sonic hedgehog signaling molecule.