Table 2.

Surface markers on CSLCs: potential molecular targets on the ovarian cancer CSLCs

Target molecules	Inhibitor	Phenotype of targeted cells	Effect	Reference
ZEB2	miR-200a	CD133/1+	Reduction of cell migration and invasion	[23]
MEK	U0126	Ovcar CD133+/CD44+/CD117+	Inhibition of ERK2 activation and partial suppression of cisplatin-induced EMT and CSC markers’ expression	[68]
CXCR4	AMD3100	NOY1 CD133+ cells	Inhibition of cell capacity of colony formation, migration and invasion Inhibition of tumorigenicity in vivo	[26]
ETRA – endothelin receptor A	BQ123	CD133+	Prevention of chemotherapy induced increases in tumor stem cells ETRA inhibition + chemotherapy = reduced formation of tumor spheres	[18]
CD133	Anti-CD133 toxin dCD133KDEL	NIH:OVCAR5	Inhibition of in vitro growth of NIH:OVCAR5 cells. Intraperitoneal drug therapy = decrease in tumor progression in peritoneum	[19]
CD44	nanoscale drug delivery system PI, paclitaxel synthetic analog of luteinizing hormone-releasing hormone	Metastatic CD44+ from patient ascites	Suppression of CD44 mRNA and protein, efficient induction of cell death, effective tumor shrinkage, with prevention of adverse side effects on healthy organs	[29]
Mullerian substance	Mullerian inhibiting substance-MIS or its mimetic SP600125	CD44+/CD24+/Epcam+	Shorter tumor-free intervals in vivo, enhanced migration in vitro. Inhibition of CD44+/CD24+/Epcam+ cell growth (previously enhanced by doxorubicin, cisplatin, and paclitaxel)	[39]
CD44/EpCAM	RNA-based bispecific CD44 -EpCAM aptamer	CD44+ cells	Inhibition of cell growth and induction of apoptosis. OC xenograft model: bispecific aptamer suppression of intraperitoneal tumor outgrowth more efficient than single aptamers or their combination.	[69]
LIN28	MIS or MIS mimetic SP600125	CD44+/CD24+/Epcam+/Ecad-	Decreasing colony formation Inhibition of OC cell growth by induction of G1 through cyclin-dependent kinase inhibitors	[40]
Mitochondria	Isoflavone derivative, NV-128	CD44+/MyD88+ cells	Depression of mitochondrial function and reduction of aggressive phenotype	[35]
CD44+	Conventional therapy and fusion cells (CD+ OCIC)	CD44+ cells	Activation of T cells to express elevated levels of IFN-γ with enhanced killing of CD44+ OVCA cells	[30]
Claudie-4	Clostridium perfringens enterotoxin (CPE)	CD44+ cells	Intraperitoneal administration of sublethal doses of CPE in mice harboring xenograft=significant inhibitory effect on tumor progression: cure and/or long-term survival of all treated animals	[43]
CD44	miR-199a	CD44+/CD117+ OCICs	Increase of chemosensitivity of ovarian CICs to cisplatin, paclitaxel, Adriamycin; reduction of ABCG2 and stemness markers’ expression; suppression of xenograft tumor growth	[44]
Survival-promoting mitochondria complex of hexokinase II and VDAC	3bromopyruvate	SKOV3 CD44+/CD117+/ALDH1+ cells	Sensitivity to combination treatment with significantly lowered doses of cisplatin	[32]
ETRA/ETRB	Macitentan or combination of ETRA & ETRB antagonists BQ123 & BQ788	CD133+ CSLCs	No enhancement of antitumor immune cell recruitment. In vitro prevention of ICAM 1 induction. Prevention of chemotherapy-induced increases in tumor stem cells. Macitentan alone= non-significant anti-tumor activity in vivo ą-combined with chemotherapy= reduction of tumor growth (CD133+ CSCs) combined with chemotherapy = reduction of sphere formation	[18]
IL-17 and its downstream pathways NF-kB and p38 MAPK signaling pathways	IL-17R-neutralizing antibody PDTC and SB203580	CD133+ A2780 cells	Sphere reduction	[21]