PDGF-CC underlies resistance to VEGF-A inhibition and combinatorial targeting of both suppresses pathological...

Area of Science:

• Ophthalmology
• Oncology
• Vascular Biology

Background:

• Anti-vascular endothelial growth factor A (VEGF-A) therapies are standard treatments for neovascular diseases.
• Mechanisms of resistance and non-responsiveness to anti-VEGF-A therapy are not fully understood.
• Pathological angiogenesis underlies various neovascular diseases, including certain eye conditions and cancers.

Purpose of the Study:

• To investigate the mechanisms behind resistance to anti-VEGF-A therapy.
• To identify potential therapeutic targets for improving treatment outcomes in neovascular diseases.
• To evaluate the efficacy of combined anti-VEGF-A and anti-platelet-derived growth factor C (PDGF-CC) targeting.

Main Methods:

• Utilized various in vitro and in vivo model systems to study pathological angiogenesis.
• Assessed the effects of VEGF-A inhibition on PDGF-CC and its receptors.
• Compared the efficacy of monotherapy versus combination therapy targeting VEGF-A and PDGF-CC.

Main Results:

• Inhibition of VEGF-A led to direct upregulation of PDGF-CC and its receptors in multiple cell types.
• This upregulation was observed in both in vitro and in vivo models of pathological angiogenesis.
• Combined targeting of VEGF-A and PDGF-CC demonstrated superior suppression of pathological angiogenesis compared to monotherapy.

Conclusions:

• Compensatory upregulation of PDGF-CC may contribute to resistance against anti-VEGF-A therapy.
• Combined inhibition of VEGF-A and PDGF-CC offers a promising therapeutic strategy for neovascular diseases.
• This combinatorial approach may overcome resistance and enhance treatment efficacy.