Targeting the tumor stroma in hepatocellular carcinoma

Table 1 Overview of clinical trials that focus on the tumor environment of hepatocellular carcinoma

	Drug	Targets	Trial	Phase	Status	Ref.
Tyrosine kinase inhibitors	Sorafenib	PDGFR	NCT00105443	III	Completed1	[90]
		VEGFR
		RAF/MEK/ERK
	Orantinib	PDGFR, FGFR	NCT02178358	I/II	Completed	[91]
		VEGFR
	Sunitinib	VEGFR	NCT00699374	III	Terminated	[71]
		PDGFR	NCT00514228	II	Completed	[70]
		RET	NCT00361309	II	Completed	[69]
		CSF	NCT00428220	N/A	Ongoing
	Linifanib	VEGF, PDGF, PDGFR-β, KDR	NCT01009593	III	Terminated
		CSF	NCT00517920	II	Completed	[68]
	Brivanib	VEGFR	NCT00858871	III	Completed	[59]
		FGFR	NCT00908752	III	Ongoing
			NCT00825955	III	Ongoing
			NCT01108705	III	Terminated
			NCT00355238	II	Completed	[92]
			NCT00437424	I	Completed	[93]
	Cediranib	VEGFR	NCT00238394	II
			NCT00427973	II	Terminated	[54]
	Dovitinib	VEGFR, PDGFR, FGFR	NCT01232296	II	Ongoing
Antibodies	Bevacizumab	VEGF	NCT00335829	II	Completed	[94]
			NCT00162669	II	Completed	[50]
			NCT00605722	II	Completed	[51]
			NCT00049322	II	Completed	[52]
			NCT00280007	II	Terminated
			NCT01180959	II	Ongoing
	Ramucirumab	VEGFR	NCT00627042	II	Completed	[53]
			NCT01140347	III	Ongoing
	GC33	Glypican-3	NCT01507168	II	Completed
			NCT00746317	I	Completed	[84]
			NCT00976170	I	Ongoing
Other kinase inhibitors	Temsirolimus	mTOR	NCT01008917	I	Ongoing
			NCT01687673	II	Recruiting
	Everolimus	mTOR	NCT01035229	III	Completed	[95]
			NCT01488487	II	Ongoing
			NCT00516165	I/II	Completed	[66]
			NCT00828594	I	Terminated
	LY2157299	TGF-βR1	NCT01246986	II	Recruiting
			NCT02178358	II	Recruiting
	PI-88	Heparanase	NCT00568308	III	Terminated
			NCT01402908	III	Ongoing
			NCT00247728	II	Completed	[30]
	Zoledronic acid	Macrophages	NCT01259193	II	Ongoing

¹Sorafenib is currently used as the standard-of-care for advanced hepatocellular carcinoma. CSF: Colony stimulating facto-1-receptor; mTOR: Mammalian target of rapamycin.