Systems biology of pro-angiogenic therapies targeting the VEGF system

Targeting the pro-angiogenic forms of VEGF or inhibiting their expression as anti-cancer strategies

Tumor growth relies on oxygen and blood supply depending on neo-vascularization. This process is mediated by the Vascular Endothelial Growth Factor (VEGF) in many tumors. This paradigm has led to the development of specific therapeutic approaches targeting VEGF or its receptors. Despite their promising effects, these strategies have not improved overall survival of patients suffering from diffe...

Clinical Application of Therapies Targeting VEGF

This year's Lasker DeBakey Clinical Research Award goes to Napoleone Ferrara for the discovery of vascular endothelial growth factor (VEGF) as a major mediator of angiogenesis and for the development of an effective anti-VEGF therapy for wet macular degeneration, a leading cause of blindness in the elderly.

Evidence for Pro-angiogenic Functions of VEGF-Ax

The VEGF-A isoforms play a crucial role in vascular development, and the VEGF signaling pathway is a clinically validated therapeutic target for several pathological conditions. Alternative mRNA splicing leads to the generation of multiple VEGF-A isoforms, including VEGF165. A recent study reported the presence of another isoform, VEGF-Ax, arising from programmed readthrough translation. Compar...

The cytoprotective drug amifostine modifies both expression and activity of the pro-angiogenic factor VEGF-A

BACKGROUND Amifostine (WR-2721, delivered as Ethyol) is a phosphorylated aminothiol compound clinically used in addition to cis-platinum to reduce the toxic side effects of therapeutic treatment on normal cells without reducing their efficacy on tumour cells. Its mechanism of action is attributed to the free radical scavenging properties of its active dephosphorylated metabolite WR-1065. Howeve...

Direct Effects of Anti-Angiogenic Therapies on Tumor Cells: A Focus on the VEGF Signaling