VEGF / VEGFR
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work. This dossier gathers the 16 products (13 approved), 42 trials, 9 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.
Biology
VEGF is an endothelial growth factor that is also immunosuppressive in the tumour microenvironment.
- Tumour vasculature across solid tumours
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| 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.
Products by modality and phase
Browse products →| Modality | Approved | Phase 3 | Withdrawn or failed |
|---|---|---|---|
| Small molecule 11 | — | ||
| Antibody 4 | — | ||
| Bispecific antibody 1 | — | — |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| 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-012 NCT04736706 | 3 | Negative | Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab) | Primary endpoint not met (ASCO GU 2026). | |
| 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. | |
| 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). | |
| 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. | |
| 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). | |
| 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. | |
| PARADIGM NCT02394795 | 3 | Positive | First-line RAS wild-type metastatic colorectal cancer: panitumumab + mFOLFOX6 vs bevacizumab + mFOLFOX6 | OS 37.9 vs 34.3 months (HR 0.82) in left-sided RAS wild-type disease. | |
| CLEAR (KEYNOTE-581) NCT02811861 | 3 | Positive | Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm) | PFS 23.9 vs 9.2 months (HR 0.39); OS HR 0.79. | |
| KEYNOTE-775 / Study 309 NCT03517449 | 3 | Positive | Advanced endometrial cancer after platinum: lenvatinib + pembrolizumab vs doxorubicin or weekly paclitaxel | OS 18.3 vs 11.4 months (HR 0.62). | |
| KEYNOTE-826 NCT03635567 | 3 | Positive | Persistent, recurrent, or metastatic cervical cancer, first line: pembrolizumab + platinum-paclitaxel ± bevacizumab vs placebo + chemotherapy ± bevacizumab | OS 26.4 vs 16.8 months (HR 0.63), all comers. | |
| CheckMate 548 & CheckMate 143 & CheckMate 498 NCT02667587 | 3 | Negative | Glioblastoma: nivolumab added to standard therapy (newly diagnosed, MGMT-methylated CM548; MGMT-unmethylated vs temozolomide CM498) and nivolumab vs bevacizumab at recurrence (CM143) | No OS benefit in any of the three trials. | |
| CheckMate 9ER NCT03141177 | 3 | Positive | Untreated advanced clear-cell RCC: nivolumab + cabozantinib vs sunitinib | PFS HR 0.51; OS HR 0.77 at ~4 years (46.5 vs 36.0 months). | |
| IMbrave150 NCT03434379 | 3 | Positive | First-line unresectable HCC: atezolizumab + bevacizumab vs sorafenib | OS 19.2 vs 13.4 months, HR 0.66. | |
| SANET-ep and SANET-p NCT02588170 | 3 | Positive | Progressive extra-pancreatic (n=198) and pancreatic (n=172) NETs: surufatinib vs placebo (China) | PFS HR 0.33 (ep), 0.49 (p). | |
| KEYNOTE-426 NCT02853331 | 3 | Positive | Untreated advanced clear-cell RCC: pembrolizumab + axitinib vs sunitinib | OS HR 0.84 final (47.2 vs 40.8 months); PFS HR 0.69. | |
| LUME-Meso NCT01907100 | 3 | Negative | Epithelioid pleural mesothelioma, first line: cisplatin-pemetrexed ± nintedanib | PFS HR 1.01, negative. | |
| PAOLA-1 / ENGOT-ov25 NCT02477644 | 3 | Positive | Newly diagnosed advanced ovarian cancer already on bevacizumab maintenance: adding olaparib vs placebo | PFS HR 0.59 overall, 0.33 HRD-positive; 5-year OS 65.5% vs 48.4% in HRD-positive. | |
| CELESTIAL NCT01908426 | 3 | Positive | HCC after sorafenib (up to two prior lines): cabozantinib vs placebo | OS 10.2 vs 8.0 months, HR 0.76. | |
| CheckMate 214 NCT02231749 | 3 | Positive | Untreated advanced clear-cell RCC: nivolumab + ipilimumab vs sunitinib | 8-year OS HR 0.72 (ITT), 0.69 (intermediate/poor risk). | |
| REFLECT NCT01761266 | 3 | Positive | First-line unresectable HCC: lenvatinib vs sorafenib (non-inferiority) | OS 13.6 vs 12.3 months, non-inferior (HR 0.92). | |
| RESORCE NCT01774344 | 3 | Positive | HCC progressing on sorafenib: regorafenib vs placebo | OS 10.6 vs 7.8 months, HR 0.63. | |
| SARAH and SIRveNIB NCT01482442 | 3 | Negative | Locally advanced HCC: yttrium-90 radioembolisation vs sorafenib | OS not improved; fewer adverse events. | |
| MAPS NCT00651456 | 3 | Positive | Unresectable pleural mesothelioma, first line: cisplatin-pemetrexed ± bevacizumab | OS 18.8 vs 16.1 months, HR 0.77. | |
| SELECT NCT01321554 | 3 | Positive | Radioiodine-refractory differentiated thyroid cancer with progression: lenvatinib vs placebo | PFS 18.3 vs 3.6 months; HR 0.21. | |
| RAINBOW NCT01170663 | 3 | Positive | Second-line advanced gastric/GEJ cancer: ramucirumab + paclitaxel vs paclitaxel | OS 9.6 vs 7.4 months, HR 0.81. | |
| DECISION NCT00984282 | 3 | Positive | Radioiodine-refractory differentiated thyroid cancer: sorafenib vs placebo | PFS 10.8 vs 5.8 months; HR 0.59. | |
| GOG-0218 & ICON7 (bevacizumab) NCT00262847 | 3 | Mixed | Newly diagnosed advanced ovarian cancer: carboplatin-paclitaxel ± bevacizumab with bevacizumab maintenance | GOG-0218 PFS 14.1 vs 10.3 months (HR 0.72); no OS benefit. | |
| CRYSTAL & FIRE-3 | 3 | Positive | First-line metastatic colorectal cancer: FOLFIRI ± cetuximab (CRYSTAL); FOLFIRI + cetuximab vs FOLFIRI + bevacizumab (FIRE-3) | CRYSTAL KRAS-WT OS 23.5 vs 20.0 months; FIRE-3 OS 28.7 vs 25.0 months. | |
| SHARP NCT00105443 | 3 | Positive | Advanced HCC, Child-Pugh A, no prior systemic therapy: sorafenib vs placebo | OS 10.7 vs 7.9 months, HR 0.69. |
Resistance routes that involve this target
Unaddressed routes →MDSCs, M2 macrophages, and VEGF suppress T-cell function and dendritic-cell maturation.
- PD-1 + VEGF blockade; PD-1×VEGF bispecifics
Pathways where it is a node
Pathway-to-drug matrix →- Cold tumours: immune deserts and exclusionNode: Abnormal vessels (VEGF) · 6 druggable nodes
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 → - Intravasation & circulating tumour cellsNode: Leaky vessels (VEGF) · 2 druggable nodes
Getting into the bloodstream and surviving there is brutal: 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 → - Myeloid suppression: TAMs, MDSCs & don't-eat-me signalsNode: CSF1, CCL2, G-CSF, VEGF · 4 druggable nodes
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 → - The angiogenic switch & tumour vesselsNode: VEGF, FGF2, ANG2, PDGF · 3 druggable nodes
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 → - The cancer-immunity cycleNode: 5 Infiltration · 3 druggable nodes
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 → - The pre-metastatic nicheNode: VEGF, G-CSF, LOX, S100A8/9 · 3 druggable nodes
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 → - Tumour microenvironment (TME)Node: Abnormal vessels (VEGF) · 5 druggable nodes
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 → - VEGF angiogenesisNode: VEGF-A · 2 druggable nodes
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 → - VHL / HIF oxygen sensingNode: VEGF, CAIX, GLUT1, cyclin D1 · 2 druggable nodes
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 →
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →- HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer · The Lancet 2025
- CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer · New England Journal of Medicine 2021
- IMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver cancer · New England Journal of Medicine 2020
- PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours · New England Journal of Medicine 2019
Query for this target: (TITLE:"VEGF / VEGFR" OR ABSTRACT:"VEGF / VEGFR" OR TITLE:"VEGFA" OR ABSTRACT:"VEGFA" OR TITLE:"KDR" OR ABSTRACT:"KDR") 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.
Export
The dossier as machine-readable 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 4.0.