Angiogenesis and VEGF
A tumour cannot grow past a couple of millimetres without new blood vessels. VEGF calls them in; the result is a leaky, chaotic network that starves the tumour, blocks drugs and lets cells escape. Anti-VEGF drugs cancel the order and, at the right dose, straighten the roads that remain.
Diagram
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
A new housing estate demanding roads. Once the developers (VEGF) outvote the planners (thrombospondin), roads are laid overnight: badly, with dead ends and potholes, so deliveries (oxygen, drugs) fail and the estate's residents can slip out onto the motorway. Anti-VEGF drugs do not close the roads; used well they make the few that remain drivable.
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.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 5, Feeding the tumour: A tumour is a construction site that never stops.
A tumour cannot grow past a couple of millimetres without new blood vessels. VEGF calls them in; the result is a leaky, chaotic network that starves the tumour, blocks drugs and lets cells escape. Anti-VEGF drugs cancel the order and, at the right dose, straighten the roads that remain.
The angiogenic switch & tumour vessels. A tumour cannot grow beyond a couple of millimetres without its own blood supply. The 'switch' flips when the signals calling for new vessels (VEGF, FGF, angiopoietin) outweigh the ones holding them back (thrombospondin). The vessels that result are leaky and chaotic, which starves the tumour of oxygen, blocks drugs, and gives cancer cells a way out.
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.
The molecular players
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
The receptor that macrophages depend on; blocking it shrinks tenosynovial giant cell tumour (a CSF1-driven tumour) and depletes tumour-supporting macrophages, though the latter has not yet helped patients with common cancers.
A master switch that kidney cancer cells leave permanently on when they lose the VHL gene; belzutifan blocks it.
Where medicines act
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
- AxitinibApprovedRenal cell carcinomaClear cell renal cell carcinomaAdenoid cystic carcinoma
- BevacizumabApprovedColorectal cancerOvarian cancerNon-small-cell lung cancer
- CabozantinibApprovedHepatocellular carcinomaAdvanced hepatocellular carcinoma (BCLC C)Renal cell carcinoma
- IvonescimabApprovedNon-small-cell lung cancerColorectal cancerTriple-negative breast cancer (TNBC)
- LenvatinibApprovedHepatocellular carcinomaAdvanced hepatocellular carcinoma (BCLC C)Intermediate hepatocellular carcinoma (BCLC B)
- RamucirumabApprovedHepatocellular carcinomaGastric & gastro-oesophageal junction cancerNon-small-cell lung cancer
- AnlotinibApprovedNon-small-cell lung cancerSmall-cell lung cancerSarcomas (soft tissue, bone, GIST)
- Bevacizumab (glioblastoma use)ApprovedGlioma & glioblastoma
- +21 more at VEGF / VEGFR →
Open questions
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
- Is the benefit of PD-1×VEGF bispecifics due to the VEGF arm, the dose, or the format?
- Can vascular normalisation be timed and measured in patients?
- early clinicalclinicUse imaging to find the window when tumour blood vessels are working properly
Low doses of anti-blood-vessel drugs briefly make tumour vessels work better, which helps immune cells and other drugs get in. Scans can find that window for each patient.
- early clinicalWhat actually holds T cells at the tumour border?
In immune-excluded tumours T cells reach the border but cannot get in, held back by fibroblasts, matrix, abnormal vessels, CXCL12 gradients or myeloid cells, and TGF-β drugs on their own have failed. If single-cell and spatial profiling can show which stromal programme dominates in each tumour, matching the drug (TGF-β, FAP, CXCR4 or VEGF) to it could let immunotherapy work.
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2025rctHARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancerThe Lancet
- 2021rctCLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancerNew England Journal of Medicinechanged practice
- 2020rctIMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver cancerNew England Journal of Medicinechanged practice
- 2019rctPAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumoursNew England Journal of Medicinechanged practice
- 2004rctHurwitz 2004: bevacizumab with chemotherapy for metastatic colorectal cancer, the first anti-angiogenic drug to extend lifeNew England Journal of Medicinechanged practice
- 2003reviewTumorigenesis and the angiogenic switchNature Reviews Cancer
- 2000reviewThe Hallmarks of Cancer: six capabilities every tumour must acquireCell
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 5.5 of 56.