Angiogenesis in Acute Myeloid Leukemia and Opportunities for Novel Therapies

Table 1

Vascular targeting strategies for patients with acute myeloid leukemia.

Agent	References	Target	Phase of clinical study	# of Patients in AML trial(s)	Clinical activity
Bevacizumab	[34, 35]	VEGF-A	Phase 2	48, 9	None as monotherapy; minimal when combined with chemotherapy
Aflibercept	[36]	VEGF-A, VEGF-B, PlGF	Preclinical
Sunitinib	[37]	VEGFR-1,-2,-3, PDGFRs, c-KIT, FLT3, CSF-1, RET	Phase 1	15	Minimal as monotherapy
Semaxanib	[38]	VEGFR-1, -2, c-KIT, FLT3	Phase 2	6	Minimal as monotherapy
Sorafenib	[39–41]	FLT3, VEGFR-2, -3, PDGFR, Raf, c-KIT	Phase 3	127	None
Axitinib	[42]	VEGFR-1, -2, -3, PDGFR-β, c-KIT	Phase 2	12	Minimal as monotherapy
Cediranib	[37]	VEGFR-1, -2, -3, PDGFR-β, c-KIT	Phase 1	35	Modest as monotherapy
Vatalinib	[43]	VEGFR-1, -2, -3, PDGFR-β, c-KIT, FMS	Phase 1	17	None with monotherapy; minimal when combined with chemotherapy
Combretastatin A-4-Phosphate (Zybrestat)	[44]	Microtubule depolymerization in endothelial cells, direct cytotoxicity to AML cells	Preclinical
Combretastatin A-1-Phosphate (OXi4503)	[15]	Microtubule depolymerization in endothelial cells, direct cytotoxicity to AML cells	Phase 1	Ongoing