Targeting cancer stem cells in drug discovery: Current state and future perspectives

Table 1 Agents targeting the Wnt signaling pathway in clinical trials

Compound	Target/mechanism	Tumor type	Highest phase	Organization
LGK974[53]	Porcupine inhibitor	Melanoma; breast cancer; pancreatic cancer	Phase I	Novartis
ETC-159[54]	Porcupine inhibitor	Solid tumors	Phase I	ETC/Duke-NUS
PRI-724[55]	β-catenin/CBP	Myeloid leukemia	Phase I/II	Prism/Eisai Pharmaceuticals
XAV939[59]	Tankyrase 1 and 2 inhibitor	-	Preclinical	Novartis
IWR1[61]	Tankyrase 1 and 2 inhibitor	-	Preclinical	Tocris Bioscience
JW74[70]	Tankyrase 1 and 2 inhibitor	-	Preclinical	Tocris Bioscience
NSC668036[71]	Disheveled	-	Preclinical	Tocris Bioscience
OMP-18R5[64] (Vantictumab)	Frizzled receptor	Solid tumors; breast cancer; non-small cell lung cancer; pancreatic cancer	Phase I/Ib	OncoMed Pharmaceuticals
OMP-54F28[65] (Ipafricept)	Fzd8-Fc fusion protein	Solid tumors; hepatocellular carcinoma; ovarian cancer; pancreatic cancer	Phase I/Ib	OncoMed Pharmaceuticals

Table 2 Agents targeting the Notch signaling pathway in clinical trials

Compound	Target/mechanism	Tumor type	Highest phase	Organization
MK-0752	γ-secretase inhibitor	Breast cancer	Phase I	Merck
LY-900009	γ-secretase inhibitor	Metastatic cancer/lymphoma	Phase I	Perrigo and Lilly
Crenigacestat	Notch signaling inhibitor	T-cell acute lymphoblastic leukemia	Phase I/II	Lilly
CB-103	Notch signaling inhibitor	Solid tumors; hematologic cancers	Phase I/II	Cellestia Biotech
LY-3056480	Notch signaling inhibitor	Sensorineural hearing loss	Phase I/II	Lilly
RO4929097	γ-secretase inhibitor	Kidney cancer; pancreatic cancer; metastatic cancer; prostate cancer; glioblastoma multiforme; metastatic melanoma	Phase II	SpringWorks Therapeutics
BMS-906024	Notch signaling pathway	Adenoid cystic carcinoma	Phase II	Bristol-Myers Squibb
Nirogacestat	γ-secretase inhibitor	Desmoid tumors	Phase II	SpringWorks Therapeutics
Enoticumab	Anti-DLL4	Advanced solid malignancies	Phase I	Regeneron and Sanofi

Table 3 Agents targeting the Smoothened protein in clinical development

Compound	Target/mechanism	Cancer type	Highest phase	Organization
Vismodegib (GDC-0449)	Smo	Basal cell carcinoma	Launched	Roche
Sonidegib (NVP-LDE225)	Smo	Basal cell carcinoma	Launched	Novartis
Glasdegib	Smo	AML	Launched	Pfizer
Patidegib	Smo	Basal cell nevus syndrome; skin cancer	Phase II	PellePharm
BMS-833923	Smo	Leukemia	Phase II	Bristol-Myers Squibb
Taladegib	Smo	Esophageal cancer; gastroesophageal junction cancer; solid tumors; small cell lung carcinoma	Phase I/II	Ignyta
G-024856	Smo	Basal cell carcinoma	Phase I	Roche
LEQ-506	Smo	Advanced solid tumors	Phase I	Novartis

Smo: Smoothened.