# VEGF angiogenesis

Source: https://onco.cc/pathways/vegf-angiogenesis/  
OnCo record `vegf-angiogenesis` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pathway
- Last checked: 2026-09-04
- 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.
- 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Angiogenesis
- Wikipedia: https://en.wikipedia.org/wiki/Angiogenesis

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Kaposi sarcoma](https://onco.cc/cancers/kaposi-sarcoma/), [Mesothelioma](https://onco.cc/cancers/mesothelioma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Osteosarcoma](https://onco.cc/cancers/osteosarcoma/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)](https://onco.cc/cancers/vascular-tumours/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/)
- targets: [HIF-2α](https://onco.cc/targets/hif2a/), [PD-1](https://onco.cc/targets/pd1/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Anlotinib](https://onco.cc/drugs/anlotinib/), [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Belzutifan](https://onco.cc/drugs/belzutifan/), [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Bevacizumab (glioblastoma use)](https://onco.cc/drugs/bevacizumab-glioma/), [Donafenib](https://onco.cc/drugs/donafenib/), [Ivonescimab](https://onco.cc/drugs/ivonescimab/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Ramucirumab](https://onco.cc/drugs/ramucirumab/), [Rivoceranib (apatinib)](https://onco.cc/drugs/rivoceranib/)
- key papers: [Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014/)
- pairings: [PD-1 blockade + VEGF inhibition](https://onco.cc/pairings/io-plus-vegf/)
- ideas: [Use imaging to find the window when tumour blood vessels are working properly](https://onco.cc/ideas/idea-bio2-vascular-normalisation-window/)
- pathways: [Bladder cancer (KEGG map)](https://onco.cc/pathways/bladder-cancer-signalling/), [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Glioma (KEGG map)](https://onco.cc/pathways/glioma-signalling/), [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [Proteoglycans in cancer](https://onco.cc/pathways/proteoglycans-in-cancer/), [Renal cell carcinoma (KEGG map)](https://onco.cc/pathways/renal-cell-carcinoma-signalling/), [The angiogenic switch & tumour vessels](https://onco.cc/pathways/angiogenic-switch/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- terms: [Angiogenesis](https://onco.cc/terms/angiogenesis/), [Growth factor](https://onco.cc/terms/growth-factor/), [Hallmark: inducing or accessing vasculature](https://onco.cc/terms/inducing-angiogenesis/), [Hallmarks of cancer as a synthesis of the theories](https://onco.cc/terms/hallmarks-synthesis/), [Mechanical theory: stiffness, pressure and force as causes](https://onco.cc/terms/mechanical-theory-of-cancer/), [Microenvironment and inflammation: tumours as wounds that do not heal](https://onco.cc/terms/microenvironment-inflammation-theory/)

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