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The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work. This dossier gathers the 29 products (22 approved), 582 trials, 12 pathways and 1 resistance route in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
VEGF is an endothelial growth factor that is also immunosuppressive in the tumour microenvironment.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Renal cell carcinoma | >90% | Clear-cell VHL loss drives VEGF (pathway prevalence) | cBioPortal (TCGA) | |
| Hepatocellular carcinoma | n/a | Angiogenic dependency; no selection biomarker | Wikipedia | |
| Colorectal cancer | n/a | No selection biomarker for bevacizumab | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Approved | Phase 3 | Phase 2 | Withdrawn or failed |
|---|---|---|---|---|
| Small molecule 19 | ||||
| Antibody 4 | - | - | - | |
| Bispecific antibody 4 | - | |||
| Recombinant fusion protein 1 | - | - | - | |
| Small-molecule VEGFR2 TKI 1 | - | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
MOUNTAINEER-03 NCT05253651 | 3 | Recruiting | First-line HER2-positive, RAS wild-type metastatic colorectal cancer: tucatinib with trastuzumab and mFOLFOX6 against mFOLFOX6 with bevacizumab or cetuximab | - | |
| 3 | Active | A Multi-Center, Double-Blind, Randomized, Phase III Study to Investigate the Efficacy and Safety of Nofazinlimab (CS1003) in Combination With Lenvatinib Compared to Placebo in Combination With Lenvatinib as First-Line Therapy in Subjects With Advanced Hepatocellular Carcinoma (HCC) | - | ||
CLARITY-Gastric 01 NCT06346392 | 3 | Positive | Second- or later-line CLDN18.2-positive advanced gastric/GEJ cancer: sonesitatug vedotin (AZD0901/CMG901) vs investigator's choice | Co-primary endpoints including OS met (July 2026); numbers pending. | |
EMERALD-3 NCT05301842 | 3 | Positive | Embolisation-eligible unresectable HCC: STRIDE (durvalumab + tremelimumab) + lenvatinib + TACE vs TACE | PFS HR ~0.70 (interim); OS immature. | |
HARMONi-3 NCT05899608 | 3 | Mixed | First-line metastatic squamous and non-squamous NSCLC, global: ivonescimab + chemotherapy vs pembrolizumab + chemotherapy | Interim PFS not statistically significant (May 2026); final readouts pending. | |
LITESPARK-011 NCT04586231 | 3 | Positive | Advanced clear-cell renal cell carcinoma that has progressed after anti-PD-1 or anti-PD-L1 therapy: belzutifan 120 mg plus lenvatinib 20 mg versus cabozantinib 60 mg, all oral once daily, open label, randomised 1:1 | Final progression-free survival 14.8 vs 10.7 months (hazard ratio 0.70, 95% CI 0.59 to 0.84; one-sided p<0.0001). Interim overall survival 34.9 vs 27.6 months (hazard ratio 0.85, 0.68 to 1.05; one-sided p 0.061), not statistically significant. Data cutoff 9 April 2025. | |
LITESPARK-012 NCT04736706 | 3 | Negative | Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab) | Primary endpoint not met (ASCO GU 2026). | |
| 3 | Active | Randomized Double-Blind Phase III Trial of Vitamin D3 Supplementation in Patients With Previously Untreated Metastatic Colorectal Cancer (SOLARIS) | - | ||
| 3 | Active | A Randomized Phase III Trial Assessing a Regorafenib-irinotecan Combination (REGIRI) Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients After Failure of Standard Therapies, According to the A/A Genotype of Cyclin D1 | - | ||
DESTINY-Gastric04 NCT04704934 | 3 | Positive | Second-line HER2-positive gastric/GEJ cancer after trastuzumab: T-DXd vs ramucirumab + paclitaxel | OS 14.7 vs 11.4 months, HR 0.70. | |
KEYNOTE-B96 / ENGOT-ov65 NCT05116189 | 3 | Positive | Platinum-resistant recurrent ovarian cancer, 1-2 prior lines: pembrolizumab + weekly paclitaxel ± bevacizumab vs placebo + paclitaxel ± bevacizumab | OS 18.2 vs 14.0 months in CPS ≥1 (HR 0.76); ITT OS HR 0.82. | |
| 3 | Active | A Phase 3, Randomized, Open-Label, Controlled Study of Cabozantinib (XL184) in Combination With Atezolizumab vs Second Novel Hormonal Therapy (NHT) in Subjects With Metastatic Castration-Resistant Prostate Cancer | - | ||
| 3 | Active | A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy | - | ||
| 3 | Active | A Phase 3, Interventional, Randomized, Multicenter, Open-Label Study of Ripretinib vs Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor (GIST) After Treatment With Imatinib | - | ||
CABINET (Alliance A021602) NCT03375320 | 3 | Positive | Previously treated advanced pancreatic (n=95) and extra-pancreatic (n=203) NETs: cabozantinib vs placebo | PFS HR 0.23 (pNET), 0.38 (epNET). | |
COMPASSION-16 / AK104-303 NCT04982237 | 3 | Positive | Persistent, recurrent, or metastatic cervical cancer, first line (China): cadonilimab (PD-1×CTLA-4 bispecific) + platinum-paclitaxel ± bevacizumab vs placebo + chemotherapy ± bevacizumab | OS HR 0.64; PFS HR 0.62. | |
HARMONi-2 NCT05499390 | 3 | Positive | First-line PD-L1-positive (TPS ≥1%) advanced NSCLC in China: ivonescimab vs pembrolizumab monotherapy | PFS HR 0.51; OS statistically significant (2026 announcement). | |
HARMONi-A NCT05184712 | 3 | Positive | EGFR-mutant non-squamous NSCLC after progression on an EGFR TKI, China: ivonescimab or placebo plus pemetrexed and carboplatin | PFS 7.1 vs 4.8 months, HR 0.46. | |
LEAP-012 NCT04246177 | 3 | Mixed | Unresectable non-metastatic HCC: TACE + lenvatinib + pembrolizumab vs TACE + placebo | PFS HR 0.66; final OS HR 0.98. | |
TiNivo-2 NCT04987203 | 3 | Negative | Advanced RCC after progression on a PD-1/PD-L1 inhibitor: tivozanib + nivolumab vs tivozanib | PFS HR 1.10; no benefit from nivolumab rechallenge. | |
| 3 | Active | A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Cabozantinib (XL184) in Subjects With Radioiodine-Refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy | - | ||
BEATcc / ENGOT-Cx10 / GOG-3030 NCT03556839 | 3 | Positive | Metastatic, persistent, or recurrent cervical cancer, first line: atezolizumab + cisplatin/carboplatin-paclitaxel + bevacizumab vs the same without atezolizumab | OS 32.1 vs 22.8 months (HR 0.68). | |
CAIRO5 NCT02162563 | 3 | Mixed | Initially unresectable colorectal liver metastases, stratified by sidedness and RAS/BRAF status: a doublet plus bevacizumab, FOLFOXIRI plus bevacizumab, or a doublet plus panitumumab, with central resectability review every two months | FOLFOXIRI plus bevacizumab better than a doublet for right-sided or RAS/BRAF-mutant disease; panitumumab no better than bevacizumab for left-sided wild-type disease. | |
CARES-310 NCT03764293 | 3 | Positive | First-line unresectable HCC: camrelizumab + rivoceranib vs sorafenib | OS 23.8 vs 15.2 months, HR 0.62. | |
CONTACT-03 NCT04338269 | 3 | Negative | Advanced RCC progressing on or after a PD-1/PD-L1 inhibitor: atezolizumab + cabozantinib vs cabozantinib | PFS HR 1.03; OS HR 0.94, negative. | |
DUO-O / ENGOT-ov46 NCT03737643 | 3 | Mixed | Newly diagnosed non-BRCA-mutated advanced ovarian cancer: chemotherapy + bevacizumab + durvalumab, then durvalumab + bevacizumab ± olaparib maintenance, vs standard | PFS HR 0.63; interim OS HR 0.95. | |
FRESCO-2 NCT04322539 | 3 | Positive | Refractory metastatic colorectal cancer after all standard therapies: fruquintinib vs placebo | OS 7.4 vs 4.8 months, HR 0.66. | |
SUNLIGHT NCT04737187 | 3 | Positive | Refractory metastatic colorectal cancer: trifluridine/tipiracil + bevacizumab vs trifluridine/tipiracil | OS 10.8 vs 7.5 months, HR 0.61. | |
COSMIC-313 NCT03937219 | 3 | Mixed | Untreated intermediate/poor-risk clear-cell RCC: cabozantinib + nivolumab + ipilimumab vs nivolumab + ipilimumab | PFS HR 0.73; OS HR 1.02 (no benefit). | |
LEAP-002 NCT03713593 | 3 | Negative | First-line unresectable HCC: lenvatinib + pembrolizumab vs lenvatinib | OS HR 0.84, not significant. |
MDSCs, M2 macrophages, and VEGF suppress T-cell function and dendritic-cell maturation.
KEGG's bladder cancer map shows two routes: low-grade papillary tumours driven by FGFR3 or HRAS activating the MAPK relay, and high-grade invasive tumours that lose TP53 and RB1. Erdafitinib targets the first route; antibody-drug conjugates and PD-1 antibodies now anchor treatment of the second.
Which nodes have drugs →Tumours come in three immune weathers: inflamed (T cells inside, checkpoint drugs work), excluded (T cells stuck at the edge), and desert (no T cells at all). Most common cancers are excluded or desert, and turning them 'hot' is the central problem of immunotherapy.
Which nodes have drugs →This KEGG map shows how hepatitis viruses, alcohol and aflatoxin leave the liver with mutations in telomerase, TP53, Wnt/beta-catenin, PI3K/AKT/mTOR and the oxidative stress sensor NRF2, which together drive liver cancer. It matters because the map explains why liver cancer is treated mainly with angiogenesis blockers and immunotherapy rather than a single targeted drug.
Which nodes have drugs →Getting into the bloodstream kills almost every cell that tries: cells are ripped from their neighbours, battered by flow, and hunted by NK cells. Fewer than one in a thousand survive. The ones that do travel in clusters, wear a cloak of platelets, or ride with neutrophils. Liquid biopsies catch what is left.
Which nodes have drugs →Tumours recruit the body's clean-up cells (macrophages and immature myeloid cells) and re-train them as bodyguards. They switch off T cells, build vessels, and, when a therapeutic antibody flags a cancer cell for eating, are told 'don't eat me' by CD47 on its surface.
Which nodes have drugs →KEGG's kidney cancer map shows how losing VHL lets the oxygen sensor HIF pile up and order new blood vessels (VEGF, PDGF), while MET and PI3K drive growth in other subtypes. Anti-VEGF drugs, HIF-2a inhibitors and immunotherapy all act on this circuit.
Which nodes have drugs →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.
Which nodes have drugs →Seven steps the immune system must complete to kill a tumour: release of antigens, pick-up by dendritic cells, priming of T cells in lymph nodes, travel, entry into the tumour, recognition, and killing. Every immunotherapy pushes on one step; every escape blocks one.
Which nodes have drugs →Before a single cancer cell arrives, the primary tumour sends parcels ahead: tiny vesicles (exosomes) and hormones that recruit bone-marrow cells to a distant organ and remodel it into fertile soil. By the time the seed lands, the bed is already made.
Which nodes have drugs →A tumour is not just cancer cells. It is a neighbourhood of fibroblasts, immune cells, blood vessels, nerves, and scaffolding that the cancer recruits and corrupts, and that decides whether drugs and immune cells can get in.
Which nodes have drugs →How tumours grow their own blood supply. Low oxygen makes cells release VEGF, which tells blood-vessel cells to sprout toward the tumour.
Which nodes have drugs →The VHL/HIF pathway is how cells sense oxygen (the 2019 Nobel Prize). VHL destroys HIF when oxygen is present. Kidney cancers lose VHL, so HIF-2α is permanently on and drives blood vessel growth and proliferation.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"VEGF / VEGFR" OR ABSTRACT:"VEGF / VEGFR" OR TITLE:"VEGFA" OR ABSTRACT:"VEGFA" OR TITLE:"KDR" OR ABSTRACT:"KDR" OR TITLE:"FLT1" OR ABSTRACT:"FLT1" OR TITLE:"FLT4" OR ABSTRACT:"FLT4" OR TITLE:"PGF" OR ABSTRACT:"PGF") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about VEGF / VEGFR, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/vegf.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/vegf.json. Licence CC BY-NC 4.0.