Table 1.

Therapeutic attempts to target cancer stem cell (CSC).

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.