Selected therapeutic targets on AML niche
| Mechanism | Targets | Cognate ligand in BM niche | BM niche | Drug | Clinical trials reference |
|---|---|---|---|---|---|
| Adhesion of leukemic stem cell to bone marrow niche | CD44 | Hyaluronan, osteopontin | Endosteal niche | Polymeric nanoparticle-mediated silencing of CD44 | N/R |
| Selectin E | Selectin E ligand | Vascular niche | Uproleselan | [108, 109] | |
| VLA4 | VCAM1 | Vascular niche | AS101 | N/R | |
| CXCL12/CXCR4 axis | - | CXCR4 | Vascular niche | Ulocuplumab | [108, 109] |
| Plerixafor | [119, 120] | ||||
| CXCR4 antagonist LY2510924 | [121] | ||||
| Angiogenesis | - | VEGF | Vascular niche | Aflibercept | N/R |
| Bevacizumab | [136] | ||||
| Angiopoietins | Vascular niche | Trebananib | [139] | ||
| Bone remodeling signaling pathway | - | Proteasome inhibitors | Vascular niche | Bortezomib | [143] |
| Carfilzomib | [144] | ||||
| Ixazomib | [145] | ||||
| Receptor tyrosine kinase inhibitors | Vascular niche | Cabozantinib | [146] | ||
| Bone marrow adipose tissue remodeling | - | FAO inhibitors | Vascular niche | Avocatin B | N/R |
| Tumor immune evasion | - | PD1 inhibitor | - | Nivolumab | [170] |
| Pembrolizumab | [171, 172] | ||||
| Anti-CTLA4 | - | Ipilimumab | [167] |
-: no data. N/R: no reference; VLA4: very late antigen 4; VCAM1: vascular adhesion molecule 1; VEGF: vascular endothelial growth factor; FAO: fatty acid β-oxidation; PD1: programmed death 1; CTLA4: cytotoxic T-lymphocyte associated protein 4