Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond

Table 2 Agents targeting vascular endothelial growth factor/vascular endothelial growth factor receptor under clinical investigation for the treatment of drug-resistant and metastatic colorectal cancer

Agent	Targeted molecule	Condition	Study phase	Clinical trial identifier
Vanucizumab	VEGF-A/angiopoietin-2	mCRC	Phase II	NCT02141295
Sorafenib	VEGFR	mCRC	Phase II	NCT03251612
		Previously treated mCRC	Phase II	NCT01471353
		mCRC	Phase II	NCT00826540
		KRAS-mutated mCRC	Phase II	NCT01715441
Bevacizumab	VEGF	Untreated mCRC	Phase II	NCT02141295
		Advanced CRC	Phase II	NCT02487992
Linifanib ABT-869	VEGFR	Advanced CRC	Phase II	NCT00707889
Vatalanib	VEGFR	mCRC	Phase III	NCT00056446
		mCRC	Phase III	NCT00056459
Famitinib	VEGFR2/3	Advanced CRC	Phase II	NCT01762293
Cediranib	VEGFR2	First-line mCRC	Phase III	NCT00399035
Semaxanib	VEGFR	mCRC	Phase III	NCT00004252
		Advanced CRC	Phase I/II	NCT00005818
Nintedanib	VEGFR	Refractory mCRC	Phase III	NCT02149108
Ramucirumab	VEGFR2	Chemotherapy refractory mCRC	Phase III	NCT03520946
Apatinib	VEGFR2	Refractory CRC	Phase II	NCT03190616
		mCRC	NA	NCT03743428
		End-stage CRC	Phase II	NCT02829385
Brivanib	VEGFR2	KRAS-wild-type mCRC	Phase III	NCT00640471
Regorafenib	VEGFR1/2/3	Later-lines treatment of mCRC	Phase III	NCT05328908
		mCRC	Phase III	NCT05425940
Surufatinib	VEGFR1/2/3	Advanced CRC	Phase II	NCT05372198
Lenvatinib	VEGFR1/2/3	mCRC	Phase III	NCT04776148
Fruquitinib	VEGFR tyrosine kinase	Non-MSI-H/dMMR mCRC	Phase II	NCT04866862
Vandetanib	VEGF/VEGFR	mCRC	Phase I	NCT00532090
		mCRC	Phase II	NCT00500292
		Advanced CRC	Phase I	NCT00496509

VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor; mCRC: Metastatic colorectal cancer; MSI: Microsatellite instability; dMMR: mismatch repair deficient.