{"entity":{"id":"vegf-angiogenesis","kind":"pathway","name":"VEGF angiogenesis","aka":[],"tldr":"How tumours grow their own blood supply. Low oxygen makes cells release VEGF, which tells blood-vessel cells to sprout toward the tumour.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Angiogenesis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Angiogenesis"}],"tags":[],"related":[],"cancers":["rcc","hcc","colorectal","nsclc"],"sections":[],"technologies":["antiangiogenic"],"targets":["vegf","hif2a","pd1"],"drugs":["ivonescimab","belzutifan","atezolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"analogy":"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.","nodes":[{"id":"hyp","label":"Hypoxia","x":50,"y":5},{"id":"hif","label":"HIF-1α / HIF-2α","x":50,"y":22,"targetId":"hif2a"},{"id":"vegf","label":"VEGF-A","x":50,"y":40,"targetId":"vegf"},{"id":"vegfr","label":"VEGFR2 (endothelium)","x":50,"y":58},{"id":"sig","label":"PLCγ / MAPK / PI3K","x":50,"y":74},{"id":"ang","label":"Angiogenesis, permeability","x":25,"y":92},{"id":"imm","label":"Immune suppression (DC, Treg)","x":75,"y":92}],"edges":[{"from":"hyp","to":"hif","type":"activates"},{"from":"hif","to":"vegf","type":"activates"},{"from":"vegf","to":"vegfr","type":"activates"},{"from":"vegfr","to":"sig","type":"activates"},{"from":"sig","to":"ang","type":"activates"},{"from":"vegf","to":"imm","type":"activates"}],"interventions":["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"]},"route":"/pathways/vegf-angiogenesis/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"kaposi-sarcoma","kind":"cancer","name":"Kaposi sarcoma","route":"/cancers/kaposi-sarcoma/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"vascular-tumours","kind":"cancer","name":"Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)","route":"/cancers/vascular-tumours/"}],"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"}],"target":[{"id":"hif2a","kind":"target","name":"HIF-2α","route":"/targets/hif2a/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"anlotinib","kind":"drug","name":"Anlotinib","route":"/drugs/anlotinib/"},{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"belzutifan","kind":"drug","name":"Belzutifan","route":"/drugs/belzutifan/"},{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"bevacizumab-glioma","kind":"drug","name":"Bevacizumab (glioblastoma use)","route":"/drugs/bevacizumab-glioma/"},{"id":"donafenib","kind":"drug","name":"Donafenib","route":"/drugs/donafenib/"},{"id":"ivonescimab","kind":"drug","name":"Ivonescimab","route":"/drugs/ivonescimab/"},{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"ramucirumab","kind":"drug","name":"Ramucirumab","route":"/drugs/ramucirumab/"},{"id":"rivoceranib","kind":"drug","name":"Rivoceranib (apatinib)","route":"/drugs/rivoceranib/"}],"paper":[{"id":"paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014","kind":"paper","name":"Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma","route":"/key-papers/paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014/"}],"pairing":[{"id":"io-plus-vegf","kind":"pairing","name":"PD-1 blockade + VEGF inhibition","route":"/pairings/io-plus-vegf/"}],"idea":[{"id":"idea-bio2-vascular-normalisation-window","kind":"idea","name":"Use imaging to find the window when tumour blood vessels are working properly","route":"/ideas/idea-bio2-vascular-normalisation-window/"}],"pathway":[{"id":"bladder-cancer-signalling","kind":"pathway","name":"Bladder cancer (KEGG map)","route":"/pathways/bladder-cancer-signalling/"},{"id":"colorectal-cancer-signalling","kind":"pathway","name":"Colorectal cancer (KEGG map)","route":"/pathways/colorectal-cancer-signalling/"},{"id":"glioma-signalling","kind":"pathway","name":"Glioma (KEGG map)","route":"/pathways/glioma-signalling/"},{"id":"hepatocellular-carcinoma-signalling","kind":"pathway","name":"Hepatocellular carcinoma (KEGG map)","route":"/pathways/hepatocellular-carcinoma-signalling/"},{"id":"proteoglycans-in-cancer","kind":"pathway","name":"Proteoglycans in cancer","route":"/pathways/proteoglycans-in-cancer/"},{"id":"renal-cell-carcinoma-signalling","kind":"pathway","name":"Renal cell carcinoma (KEGG map)","route":"/pathways/renal-cell-carcinoma-signalling/"},{"id":"angiogenic-switch","kind":"pathway","name":"The angiogenic switch & tumour vessels","route":"/pathways/angiogenic-switch/"},{"id":"cancer-immunity-cycle","kind":"pathway","name":"The cancer-immunity cycle","route":"/pathways/cancer-immunity-cycle/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"term":[{"id":"angiogenesis","kind":"term","name":"Angiogenesis","route":"/terms/angiogenesis/"},{"id":"growth-factor","kind":"term","name":"Growth factor","route":"/terms/growth-factor/"},{"id":"inducing-angiogenesis","kind":"term","name":"Hallmark: inducing or accessing vasculature","route":"/terms/inducing-angiogenesis/"},{"id":"hallmarks-synthesis","kind":"term","name":"Hallmarks of cancer as a synthesis of the theories","route":"/terms/hallmarks-synthesis/"},{"id":"mechanical-theory-of-cancer","kind":"term","name":"Mechanical theory: stiffness, pressure and force as causes","route":"/terms/mechanical-theory-of-cancer/"},{"id":"microenvironment-inflammation-theory","kind":"term","name":"Microenvironment and inflammation: tumours as wounds that do not heal","route":"/terms/microenvironment-inflammation-theory/"}]}}