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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.
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.
Shares Hallmark: inducing or accessing vasculature, Angiogenesis, Renal cell carcinoma (KEGG map), HIF-2α.
Shares Renal cell carcinoma (KEGG map), HIF-2α, The angiogenic switch & tumour vessels, Belzutifan.
Shares Hallmark: inducing or accessing vasculature, Microenvironment and inflammation: tumours as wounds that do not heal, VEGF / VEGFR, Bevacizumab.
Shares Angiogenesis, VEGF / VEGFR, Renal cell carcinoma, Hepatocellular carcinoma.
Shares Renal cell carcinoma (KEGG map), The angiogenic switch & tumour vessels, Salivary gland cancers, VEGF / VEGFR.
Shares PD-1 blockade + VEGF inhibition, Lenvatinib, VEGF / VEGFR, PD-1.
Shares Proteoglycans in cancer, Renal cell carcinoma (KEGG map), Glioma & glioblastoma, Gastric & gastro-oesophageal junction cancer.
Shares Renal cell carcinoma (KEGG map), Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma), The angiogenic switch & tumour vessels, VEGF / VEGFR.