Researchers in the Imoukhuede lab at Washington University have developed a library of mutant PDGF-B proteins to develop more effective VEGF pathway inhibitors. As PDGF-B also binds to VEGF receptors, a mutant form can be used to block VEGF binding and stop tumor angiogenesis.
Bevacizumab, a successful VEGF inhibitor, is used in a variety of cancers to prevent angiogenesis. However, its efficacy is reduced due to the cross-family receptor binding of PDGF to VEGF receptors. Blocking VEGFR2 occupancy with mutant PDGF-B is a more effective strategy to prevent angiogenesis.
Stage of Research
The researchers have developed a PDGF-B mutagenesis library and are screening potential mutants. They are specifically characterizing mutants that can inhibit VEGF receptors and do not activate PDGF receptors.
- Competitor of bevacizumab and other VEGF inhibitors
- Wide variety of cancers
- Macular degeneration
- Inhibits VEGF receptors to prevent angiogenesis
- Overcomes poor efficacy of existing VEGF inhibitors
- PDGF-B contributes significantly to VEGFR2 occupancy
- Mutant PDGF-B outcompetes for VEGFR2 binding