Angiogenesis and Its Therapeutic Opportunities

Table 4

Selected angiogenesis inhibitors in clinical trials.

Inhibiting target	Drug	Sponsor	Clinical trials/mechanism	References
Epidermal growth factor receptor (EGFR)	Gefitinib (Iressa)	AstraZeneca and Teva	FDA-approved in 2003 for NSCLC/effective in cancers with mutated and overactive EGFR	[103, 104]
	Lapatinib (Tykerb)	GSK	FDA-approved in 2007 for breast cancer/dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways	[105]
	Erlotinib (Tarceva)	Genentech/OSI pharmaceuticals/Roche	FDA-approved in 2005/used to treat nonsmall cell lung cancer, pancreatic cancer, and several other types of cancer	[106]
	Canertinib (CI-1033)	Selleck Chemicals	Phase II/irreversible tyrosine-kinase inhibitor with activity against EGFR, HER-2, and ErbB-4	[107]
VEGFR	Vatalanib (PTK787 or PTK/ZK)	Bayer Schering and Novartis	Phase III/it inhibits all known VEGF receptors, as well as platelet-derived growth factor receptor-beta and c-kit, but is most selective for VEGFR-2	[108]
VEGFR-2	IMC-1C11	ImClone Systems	Phase I/chimerized monoclonal antibody	[109]
VEGFR-3	mF4-31C1	ImClone Systems	Phase I/rat monoclonal antibody to murine VEGFR-3, which potently antagonizes the binding of VEGF-C to VEGFR-3	[110]
Multiple growth factor receptors	Imatinib (Glivec)	Novartis	FDA-approved in 2001/competitive tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably Philadelphia chromosome-positive (Ph^+) chronic myelogenous leukemia (CML)	[111]
	Sunitinib (Sutent)	Pfizer	FDA-approved in 2006 for renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST)/the simultaneous inhibition of receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs)	[112]
	Sorafenib (Nexavar)	Bayer and Onyx pharmaceuticals	FDA-approved in 2005/a small molecular inhibitor of several tyrosine protein kinases (VEGFR and PDGFR) and Raf kinases (more avidly C-Raf than B-Raf)	[113]
	Pazopanib (Votrient)	GlaxoSmithKline	FDA-approved in 2009 for advanced renal cancer/multitargeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit	[114]
VEGF	Bevacizumab (Avastin)	Genentech/Roche	FDA-approved in 2004 for metastatic colorectal cancer/humanized anti-VEGF mAb, licensed to treat various cancers including colorectal, lung, breast (outside the USA), glioblastoma (USA only), kidney, and ovarian	[115, 116]
Integrin𝛼𝑉𝛽3	Vitaxin	Applied molecular evolution	Phase II as a treatment for colorectal cancer/humanized monoclonal antibody against the vascular integrin 𝛼𝑉𝛽3	[117]