Novel molecular targets in hepatocellular carcinoma

Table 2 Summary of potential pipeline compounds targeting novel molecular targets in several cancers

Drug	Descriptions	Phase	Type of tumour	Ref./ClinicalTrials.gov identifier
Hh signaling pathway
Erismodegib, (LDE-225)	Smo antagonist	0	Pancreatic cancer	NCT01694589
	In vitro and in vivo test results on HCC cells are not available	I	Advanced solid tumours	NCT00880308
		I	SCLC	NCT01579929
		II	Advanced or metastatic basal cell carcinoma	NCT01327053
		I/II	Medulloblastoma	NCT01125800
Vismodegib	Smo antagonist	I	HCC and lymphoma	NCT01546519
	Promotes regression of liver fibrosis and HCC tumour growth in a murine model of primary liver cancer[138]	I	Advanced or metastatic basal cell carcinoma
		II	Ovarian cancer	NCT00739661
	Shows no obvious response in patients with hepatic impairment[139]
Notch signaling pathway
MK-0752	γ-secretase inhibitor	I	Advanced solid tumour	[63]
	In vitro and in vivo test results on HCC cells are not available	I	Brain and central nervous system tumours	[64]
RO4929097	γ-secretase inhibitor	I	Refractory metastatic or locally advanced solid tumours	[65]
	Prevents tumour development and decreases liver fibrosis in mouse model[141]
		II	Metastatic colorectal cancer	[66]
Plk1
HMN-214	Stilbene derivative interferes with the subcellular spatial distribution of Plk1 at centrosomes	I	Advanced solid tumours	[79]
	In vitro and in vivo test results on HCC cells are not available
GSK461364	Reversible ATP-competitive Plk1 inhibitor	I	Advanced solid tumours and non-Hodgkin’s lymphoma	[81]
	In vitro and in vivo test results on HCC cells are not available
Arginine deprivation
ADI-PEG-20	Arginine deiminase	I	Pediatric ASS-deficient tumour	NCT01528384
	Shows its safe and efficacious in stabilizing the progression of advanced HCC in an Asian population
		II	SCLC	[142], NCT01266018
		II	Advanced melanoma	[143]
	Shows no overall survival benefit in second line setting for patients with advanced HCC
		II	Malignant pleural mesothelioma	NCT01279967
		II/III	Advanced HCC	[87,144]
BCT100/ Peg-rhArg1	Recombinant human arginase I	I	Leukemia and lymphoma	NCT01551628
	Inhibits tumour growth of HCC xenografts in mouse model[85]
		I/II	Advanced HCC	[90], NCT01092091
HDACs
Resminostat	HDACs (1, 3 & 6) inhibitor[145]	I/II	Advanced HCC	[146]
	Combined with sorafenib shows no significant efficacy advantage over sorafenib monotherapy in patients with advanced HCC in East Asian populations	II	Hodgkin's lymphoma	NCT01037478
		I/II	Advanced colorectal carcinoma	NCT01277406
Chidamide	HDACs inhibitor (1, 2, 3 & 10)[147]	I	Advanced solid tumours and lymphomas	[148]
	Inhibits proliferation of HCC cells in vitro[95]
Panobinostat,(LBH-589)	Pan-HDAC inhibitor Inhibits tumour growth and lung metastasis of HCC xenografts in mouse model[149]	I	Prostate carcinoma	[150]
		I	Advanced solid tumours	[151]
		II	Refractory metastatic renal cell carcinoma	[152]
Glypican-3
Codrituzumab (GC33)	Anti-GPC3 monoclonal antibody	I	Advanced or metastatic HCC	[153]
	Inhibits tumour growth of HCC xenografts in mouse model[102]
	Shows no clinical benefit in advanced HCC patients who has failed prior systemic therapy

HCC: Hepatocellular carcinoma; HDAC: Histone deacetylase; Plk1: Polo-like kinase-1; SCLC: Small cell lung cancer; Smo: Proto-oncoprotein smoothened.