Table 2.

Molecular mechanisms prompting cancer stem cell resistance to standard and targeted therapies.

	Mechanism of resistance	Tumor	Molecule secreted	Drug	References
Cancer associated fibroblasts (CAFs)	GLI-2 enhanced expression	CRC	TGFβ2 , IL-6	5-FU/oxa	99
	NF-kB pathway	BC/lung	IL-6, IL-8	CIS	100
	Wnt/β-catenin pathway	head/neck	periostin	erlotinib	102
	PI3K/AKT and MAPK pathway	CRC	HGF, SDF-1, OPN	PI3K/AKT inhibitors	90, 103
	STAT3/NF-kB pathway	BC	IL-6	trastuzumab	104
Cancer associated adipocytes (CAAs)	High MVP expression levels	BC	CM from adipocytes	doxorubicin/ 5-FU/ paclitaxel	105
	MAPK pathway	BC	IL-4	arimidex/ docetaxel+BKM120	106
	AKT/MAPK pathways	BC	Leptin	5-FU	107
	MAPK and AKT pathways	CRC	Leptin	5-FU	108
	AMPK/mTOR/JNK pathways	BC	Resistin	doxorubicin	109
	Up-regulation of ABCG2	BC	CXCL1	doxorubicin	110
Endothelial cells (ECs)	Notch pathway	Lymphoma	Jagged-1	doxorubicin	111
	Notch pathway	CRC	Jagged-1	5-FU/oxa	112
	High c-Met expression levels	GBM		bevacizumab	113
	HIF/VEGF pathways	CRC	VEGF	bevacizumab	114
	Increase of intratumoral hypoxia	LLC		sunitinib	115
	VEGF-independent angiogenesis	Pancreatic cancer	FGFs	DC101 (anti-VEGFR2)	116
	VEGF-independent angiogenesis	RCC	IL-8	sunitinib	92
	NF-kB pathway	RCC	IL-6	sunitinib	117
	AXL and Met signaling	RCC		sunitinib	118