Predicted effects of antiangiogenic therapeutic strategies
Therapy . | Example(s)* . | Therapeutic strategy . | Local effect† . | Systemic effect† . |
|---|---|---|---|---|
| Antiangiogenic therapy targeting EC migration | αvβ3 integrin antagonist αvβ3-MMP binding antagonist anti-VE-cadherin Ab | Inhibition of EC migration | √√ | ‡ |
| Antiangiogenic therapy targeting angiogenic growth factor signaling | Anti-VEGFR-2 Ab VEGFR TK inhibitor | Inhibition of EC proliferation and migration; impairment of EPC mobilization | √√ | √ |
| Chemotherapy, antiangiogenic scheduling | Cyclophosphamide | Cytotoxicity to proliferating ECs and EPCs | √√ | √√ |
| Antiangiogenic therapy targeting angiogenic growth factors | Anti-VEGF Ab | Restoration of balance between angiogenesis stimulators and inhibitors | √√ | √√ |
| Combined therapy | Vinblastine and anti-VEGFR-2 Ab | Ablation of EPC subpopulation of BM; inhibition of EC proliferation and migration | √√ | √√√ |
Therapy . | Example(s)* . | Therapeutic strategy . | Local effect† . | Systemic effect† . |
|---|---|---|---|---|
| Antiangiogenic therapy targeting EC migration | αvβ3 integrin antagonist αvβ3-MMP binding antagonist anti-VE-cadherin Ab | Inhibition of EC migration | √√ | ‡ |
| Antiangiogenic therapy targeting angiogenic growth factor signaling | Anti-VEGFR-2 Ab VEGFR TK inhibitor | Inhibition of EC proliferation and migration; impairment of EPC mobilization | √√ | √ |
| Chemotherapy, antiangiogenic scheduling | Cyclophosphamide | Cytotoxicity to proliferating ECs and EPCs | √√ | √√ |
| Antiangiogenic therapy targeting angiogenic growth factors | Anti-VEGF Ab | Restoration of balance between angiogenesis stimulators and inhibitors | √√ | √√ |
| Combined therapy | Vinblastine and anti-VEGFR-2 Ab | Ablation of EPC subpopulation of BM; inhibition of EC proliferation and migration | √√ | √√√ |
Comparison of different antiangiogenic therapies and their anticipated effects on the local and systemic contributions to angiogenesis (see also Figure 1).
The examples given are the therapeutics used to determine the relevant model parameter values (see Supplemental Data, Section B.3 and Table B.3).
The relative magnitude of the effect of the therapy on each pathway is indicated by the number of checkmarks.
Antiangiogenic therapy targeting migration or adhesion may impact the EPC contribution to angiogenesis as well. However, since the adhesion molecule expression profile of EPCs has not been characterized, this effect has been neglected in the model.