Table 1.

Anti-angiogenesis drugs approved for metastatic CRC and recent clinical trials with potential new anti-angiogenesis therapeutics.

Compound	Category	Pro-Angiogenic Targets	Combination Drugs	Clinical Use	Route of Administration	Ref.
Aflibercept	”Trap”-inhibitor, recombinant fusion protein.	VEGF-A/B, PlGF	Fluoropyrimidines, folinic acid and irinotecan	Second line, after oxaliplatin; regardless K/NRAS and BRAF genotype	Intravenous	[75]
Bevacizumab	Recombinant humanized—mAb	VEGF-A	Fluoropyrimidines, folinic acid, irinotecan and/or oxaliplatin	First and second line; regardless K/NRAS and BRAF genotype	Intravenous	[75]
Famitinib	Small molecule, multiple kinase inhibitor	VEGRs, PDGFRs, c-KIT, FLT3, RET	Alone	No, experimental use	Oral	[76]
Fruquintinib	Small molecule, multiple kinase inhibitor	VEGRs	Alone	No, experimental use	Oral	[77]
Nintedanib	Small molecule, multiple kinase inhibitor	VEGFR 1-3, FGFRs, PDGFRs	5FU, folinic acid and oxaliplatin	No, experimental use	Oral	[78,79]
Regorafenib	Small molecule, multiple kinase inhibitor	KIT, RET, PDGFR, FGFR BRAF	Alone	After progression to other conventional treatments	Oral	[75]
Trebanabib	Fusion protein	ANG-1/2, TIE2	5FU, folinic acid and irinotecan	No, experimental use	Oral	[80]
Trifluridine/tipiracil	Antimetabolite	PD-ECGF	Alone	After progression to other conventional treatments	Oral	[75]
Vandetanib	Small molecule, multiple kinase inhibitor	VEGFR-2, EGFR	Irinotecan and cetuximab; capecitabine, oxaliplatin and bevacizumab	Not in use, due to unsafe toxicity profile	Oral	[81,82]
Vanucizumab	Bi-specific monoclonal antibody	VEGF-A, ANG-2	FOLFOX	No, experimental use	Intravenous	[83]
Vorinostat	Histone deacetylase inhibitors	HIF1-α	5FU	No, experimental use	Oral	[84,85]

Abbreviations: FOLFOX (fluorouracil, leucovorin and oxaliplatin); 5fluorouracil (5FU); Cell Factor receptor c-KIT (c-KIT); FMS-like tyrosine kinase-3 receptor (FLT3).