VEGF angiogenesis
How tumours grow their own blood supply. Low oxygen makes cells release VEGF, which tells blood-vessel cells to sprout toward the tumour.
Hypoxia stabilises HIF-1α/HIF-2α, which induce VEGF-A. VEGF-A binds VEGFR2 on endothelial cells → PLCγ/PKC/MAPK and PI3K/AKT → proliferation, migration, and permeability. Tumour vessels are chaotic and leaky, causing hypoxia and impaired drug and immune-cell delivery. Bevacizumab neutralises VEGF-A; VEGFR TKIs (axitinib, cabozantinib, lenvatinib) block the receptor; 'vascular normalisation' at moderate doses improves immune infiltration, the rationale for IO-VEGF combinations and PD-1×VEGF bispecifics. VEGF also suppresses dendritic cell maturation and expands Tregs.
In one picture
A growing town (tumour) that keeps sending out road-building orders (VEGF). Anti-angiogenic drugs cancel the orders; at the right dose the roads that remain are straighter and better, so police (immune cells) and supplies (drugs) get in.
Diagram
top- Bevacizumab, ramucirumab (antibodies)
- VEGFR TKIs: axitinib, cabozantinib, lenvatinib, sunitinib
- IO + VEGF combinations in RCC, HCC, endometrial cancer
- PD-1×VEGF bispecifics: ivonescimab and successors
- HIF-2α inhibitor belzutifan upstream in VHL-deficient RCC
Pages like this
not linked directly; found by shared links- PathwayVHL / HIF oxygen sensing
Shares Hallmark: inducing or accessing vasculature, Angiogenesis, Belzutifan, HIF-2α.
- ProductAxitinib
Shares The angiogenic switch & tumour vessels, Salivary gland cancers, Anti-angiogenic therapy, VEGF / VEGFR.
- PersonJudah Folkman
Shares Hallmark: inducing or accessing vasculature, Bevacizumab, Anti-angiogenic therapy, VEGF / VEGFR.
- ProductRegorafenib
Shares The angiogenic switch & tumour vessels, Osteosarcoma, Anti-angiogenic therapy, VEGF / VEGFR.
- PairingLenvatinib + pembrolizumab (pMMR endometrial cancer after platinum)
Shares PD-1 blockade + VEGF inhibition, Lenvatinib, VEGF / VEGFR, PD-1.
- ProductPazopanib
Shares The angiogenic switch & tumour vessels, Anti-angiogenic therapy, VEGF / VEGFR, Renal cell carcinoma.
- PathwayPD-1 / PD-L1 immune checkpoint & T-cell activation
Shares PD-1 blockade + VEGF inhibition, Ivonescimab, The cancer-immunity cycle, Tumour microenvironment (TME).
- InstitutionHarold C. Simmons Comprehensive Cancer Center, UT Southwestern
Shares Belzutifan, HIF-2α, Renal cell carcinoma, Non-small-cell lung cancer.