Vascular endothelial growth factor–Hypoxia-inducible factor 1-alpha (VEGF–HIF-1α) signaling axis (VEGF–HIF-1α axis)

The Vascular endothelial growth factor–Hypoxia-inducible factor 1-alpha (VEGF–HIF-1α) signaling axis is a fundamental molecular pathway that governs the cellular response to oxygen deprivation. Under hypoxic conditions, the transcription factor HIF-1α is stabilized and translocates to the nucleus, where it binds to hypoxia-response elements to induce the expression of pro-angiogenic genes, most notably VEGF. This axis is a primary driver of angiogenesis, the process of new blood vessel formation, which is essential for physiological tissue repair but also central to the progression of various malignancies and ischemic diseases. In cancer, the overactivation of this axis promotes tumor vascularization, metabolic reprogramming, and resistance to conventional therapies like radiation. Therapeutic intervention typically involves neutralizing VEGF with monoclonal antibodies or inhibiting the tyrosine kinase activity of its receptors, while newer strategies aim to directly inhibit HIF-1α stabilization or its transcriptional activity.

Other names

HIF-1α/VEGF pathwayHypoxia-inducible factor 1-alpha/Vascular endothelial growth factor signalingHypoxia signaling pathwayHIF-1α/VEGF axisHypoxia-inducible factor 1-alpha/Vascular endothelial growth factor A signaling axis

Drugs targeting this axis primarily function by neutralizing the VEGF ligand to prevent receptor binding, inhibiting the tyrosine kinase activity of VEGF receptors (VEGFR-1/2/3), or disrupting the stabilization, nuclear translocation, and transcriptional activity of the HIF-1α protein.