Improving cancer therapy by targeting cancer stem cells: Directions, challenges, and clinical results

Table 1 Commonly used Cancer Stem Cells Markers

Marker	Association with chemoresistance	Reported malignancies
CD34		Hematological malignancies (in combination with CD38)[8,36]
CD38		Hematological malignancies (in combination with CD34)[8,36]
CD24	Yes (in combination with CD44)[63]	Breast, prostate, pancreas (in combination with CD44)[15,23]
CD44	Yes (in combination with CD24)[63]	Breast, pancreas, stomach, prostate, head and neck, ovary, colon (in combination with CD24)[15,23]
CD133	Yes[24,25]	Brain, pancreas, lung, liver, prostate, stomach, colon, head and neck[15,23]
ALDH	Yes[60,61]	Breast, lung, head and neck, colon, liver, ovary[15,26]

ALDH: Aldehyde dehydrogenase.

Table 2 Pathways and drug candidates targeting cancer stem cells

Pathway	Targets	Compounds	Clinical development
Hedgehog	Smoothened	1Vismodegib[80-82]	Medulloblastoma
			Pancreatic cancer
			Hematological malignancies
Notch	γ-secretase	MK-0752[94]	Breast cancer
	DLL4	Demcizumab[88-90]	Pancreatic cancer
			NSCLC
			Ovarian cancer
		MEDI0639	Solid tumors
Wnt	β-catenin	Vantictumab[101]	Breast cancer
			Pancreatic cancer
			NSCLC
		OMP-54F28[102]	Ovarian cancer
			Pancreatic cancer
			Hepatic cancer
CXCR1/2-CXCL8	CXCR1	Reparixin[113,114]	Breast cancer
		SCH563705
	CXCR1/2
IL-6/JAK/STAT3	IL-6	2Tocilizumab
	JAK1, JAK2	3Tofacitinib
		4Chloroquine	Breast cancer[57]

¹Erivedge™, FDA and EMA approved for metastatic or locally advanced basal cell carcinoma;

²RoActemra™, FDA and EMA approved for rheumatoid arthritis;

³Xeljanz™, FDA approved for rheumatoid arthritis;

⁴FDA approved for malaria and extraintestinal amebiasis. DLL4: Delta-like ligand 4; FDA: Food and Drug Administration; NSCLC: Non-small-cell lung carcinoma; CXCR1/2-CXCL8: CXC chemokine receptor 1/2-interleukin 8; IL-6/JAK/STAT3: Interleukin 6/Janus kinase 2/Signal transducer and activator of transcription 3.