Dynamism, Sensitivity, and Consequences of Mesenchymal and Stem-Like Phenotype of Cancer Cells

Table 1

Different cancer therapeutic approaches based on CSCs and/or EMT.

CSC	EMT	Therapeutic target	Therapeutic approach	Cancer type	Development stage	References
	x	AKT/mTOR signaling pathway	Tunicamycin	Colon cancer	Preclinical (in vivo)	[87]
x	x	AKT2	siRNA	Breast cancer	Preclinical (in vivo)	[79]
x		ALOX5	Zileuton	Leukemia	Clinical (phase 1)	NCT02047149; NCT01130688
x		Bmi-1	Nigericin	Nasopharyngeal carcinoma	Preclinical (in vivo)	[88]
x		Bmi-1	shRNA	Nasopharyngeal carcinoma	Preclinical (in vivo)	[89]
	x	EGR-1	shRNA against EGR-1	Breast cancer; Lung cancer; Liver cancer	Preclinical (in vitro)	[90]
	x	EGR-1	Oxytocin	HNSCC	Preclinical (in vitro)	[91]
	x	EGR-1	Syntactic catalytic DNA	Breast cancer	Preclinical (in vivo)	[92]
	x	EGR-1	2-Benzoyloxycinnamaldehyde	Colon cancer	Preclinical (in vivo)	[93]
	x	EGR-1	siRNA	Colon cancer	Preclinical (in vivo)	[93]
x		Hedgehog signaling	Cyclopamine	Glioblastoma	Preclinical (in vivo)	[94]
	x	HMGA2	LBH589	Prostate cancer	Preclinical (in vivo)	[95]
x		IAP family	AT-406, SM-164, and TRAIL	Nasopharyngeal carcinoma	Preclinical (in vivo)	[96]
x	x	JAK 1/2	Ruxolitinib	Pancreatic cancer; Ovarian cancer	Preclinical (in vivo)	[19, 97]
x		Krüppel-like factor 5	Metformin	TNBC	Preclinical (in vivo)	[98]
	x	Lysine-specific demethylase 1	Pargyline	Prostate cancer	Preclinical (in vivo)	[99]
x		mTOR	Rapamycin	Neuroblastoma	Preclinical (in vivo)	[100]
x		n.d.	Metformin	Gastric cancer; Breast cancer; Ovarian cancer	Preclinical (in vivo)	[101–103]
x		n.d.	Salinomycin	HNSCC	Preclinical (in vitro)	[86]
x		n.d.	Salinomycin analogs	Breast cancer; Colon cancer	Preclinical (in vitro)	[104]
x		n.d.	EpCAM/CD3 antibody	Pancreatic cancer	Preclinical (in vivo)	[105]
		n.d.	Anti-CD33 antibody	Glioblastoma	Preclinical (in vivo)	[106]
x	x	n.d.	Quercetin	Pancreatic cancer	Preclinical (in vivo)	[107]
x		n.d.	All-trans retinoic acid	Gastric cancer	Preclinical (in vivo)	[108]
x		n.d.	Mithramycin	Various neoplasms	Clinical (phase 2)	NCT02859415
x		n.d.	Drug combination	Glioblastoma	Clinical (phase 1)	NCT02654964
	x	n.d.	Epirubicin + cisplatin + capecitabine	Gastric cancer	Clinical (phase 3)	NCT01697072
x		NADH dehydrogenase	DECA-14	Neuroblastoma	Preclinical (in vivo)	[100]
x	x	Nestin	shRNA	Glioblastoma; Lung carcinoma; Pancreatic cancer	Preclinical (in vivo)	[80–82, 109]
x	x	Nestin	siRNA	Pancreatic cancer	Preclinical (in vivo)	[84, 110]
x	x	p53 mutant cells	Metformin	Ovarian cancer FTPPC, pancreatic cancer	Clinical (phase 2)	NCT01579812; NCT02978547
x	x	PI3K-AKT; ERK1/2 pathways	LY294002; U0126	Breast cancer	Preclinical (in vitro)	[111]
	x	SNAIL	Trichostatin A	Lung cancer	Preclinical (in vitro)	[112, 113]
	x	Snail-p53 interaction	GN-25; GN-29	Pancreatic cancer; Lung cancer	Preclinical (in vivo)	[114]
x		STAT3	LLL12; shRNA	Breast cancer	Preclinical (in vivo)	[115]
x		STAT3	BBI608	Various cancers	Preclinical (in vivo)	[116]
x	x	STAT3	Salinomycin	Breast cancer	Preclinical (in vitro)	[85]
x	x	STAT3 pathway	Oncostatin M	Hepatocellular carcinoma	Preclinical (in vivo)	[117]
x		WNT pathway	Nigericin	Lung cancer	Preclinical (in vitro)	[118]
x	x	ZEB1	shRNA	Pancreatic cancer	Preclinical (in vivo)	[19]

n.d.: not described. ClinicalTrials.gov identifier. Abbreviations: HNSCC: head and neck squamous cell carcinoma; FTPPC: fallopian tube, primary peritoneal cancer.