Loading
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
Bevacizumab (2004) was the first anti-angiogenic. VEGFR TKIs (cabozantinib, lenvatinib, axitinib) are standard in RCC, HCC, and thyroid cancer, usually with PD-1 blockade. PD-1×VEGF bispecific ivonescimab beat pembrolizumab on PFS in NSCLC (HARMONi-2) and is the most-watched bispecific in solid tumours.
In plain words · The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
Backbone ribbon from PDB 1BJ1. RCSB PDB 1BJ1. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
VEGF is an endothelial growth factor that is also immunosuppressive in the tumour microenvironment.
29 products aim at VEGF / VEGFR: antibodies, bispecific antibodies, small molecules and other agents. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
The first head-to-head test of the PD-1 x VEGF bispecific against pembrolizumab in a Western population. Timing is our estimate from the registry record; the sponsor has not given a date. Source
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 29 medicines aimed at it (Ziv-aflibercept, PM8002, Zanzalintinib and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA VEGFA: RNA low tissue specificity; high antibody staining in 21 normal tissues; highest cancer staining colorectal cancer (11 of 12 high). HPA KDR: RNA low tissue specificity; high antibody staining in 3 normal tissues; highest cancer staining skin cancer (3 of 12 high). HPA FLT1: RNA tissue enriched (placenta 394 nTPM); high antibody staining in 2 normal tissues. HPA FLT4: RNA low tissue specificity; blood lineage lineage enriched (T-cells 4 nTPM); high antibody staining in 10 normal tissues; highest cancer staining pancreatic cancer (3 of 12 high). HPA PGF: RNA tissue enhanced (blood vessel 67 nTPM); no normal tissue stained high. HPA FLT1: RNA tissue enriched (placenta 394 nTPM); high antibody staining in 2 normal tissues. HPA FLT4: RNA low tissue specificity; blood lineage lineage enriched (T-cells 4 nTPM); high antibody staining in 10 normal tissues; highest cancer staining pancreatic cancer (3 of 12 high). Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Renal cell carcinoma, Hepatocellular carcinoma, Colorectal cancer, Lung cancer (all types), Ovarian cancer); approvals of single-target medicines aimed at it also list Salivary gland cancers, Cervical cancer, Brain and spinal cord tumours (all types), Sarcomas (soft tissue, bone, GIST) and more, not counted; Open Targets associates it with 22 specific cancer types at or above 0.5 (non-small cell lung carcinoma, colorectal cancer, breast cancer, renal cell carcinoma, cervical cancer, glioblastoma and more). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas VEGFA tissue; Human Protein Atlas KDR tissue; Human Protein Atlas FLT1 tissue; Human Protein Atlas FLT4 tissue; Human Protein Atlas PGF tissue; Open Targets ENSG00000112715 associations; Open Targets ENSG00000128052 associations
VEGF is an endothelial growth factor that is also immunosuppressive in the tumour microenvironment.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Bone marrow, Breast, Caudate, Cerebellum, Cerebral cortex, Cervix.
RNA cancer enhanced: Kidney Renal Clear Cell Carcinoma 668 pTPM.
Medium only: lymphoma.
HPA VEGFA tissue · HPA VEGFA pathology · HPA protein class: FDA approved drug targets
RNA: low tissue specificity, detected in many normal tissues.
Medium: Bronchus.
RNA cancer enhanced: Kidney Renal Clear Cell Carcinoma 27 pTPM.
Medium only: prostate cancer, urothelial cancer.
HPA KDR tissue · HPA KDR pathology · HPA protein class: CD markers, FDA approved drug targets
RNA: tissue enriched (placenta 394 nTPM), detected in many normal tissues.
Medium: Cerebral cortex, Colon, Placenta, Smooth muscle, Testis.
RNA cancer enhanced: Kidney Renal Clear Cell Carcinoma 123 pTPM.
No cancer stained high; medium in breast cancer, head and neck cancer, melanoma, ovarian cancer.
HPA FLT1 tissue · HPA FLT1 pathology · HPA protein class: FDA approved drug targets
RNA: low tissue specificity, detected in many normal tissues. Blood: lineage enriched (T-cells 4 nTPM).
Medium: Breast, Cerebral cortex, Cervix, Colon, Duodenum, Epididymis, Esophagus, Fallopian tube.
RNA cancer enhanced: Kidney Renal Clear Cell Carcinoma 21 pTPM.
Medium only: breast cancer, carcinoid, colorectal cancer, endometrial cancer.
HPA FLT4 tissue · HPA FLT4 pathology · HPA protein class: FDA approved drug targets
RNA: tissue enhanced (blood vessel 67 nTPM), detected in many normal tissues.
No normal tissue stained high.
RNA cancer enhanced: Kidney Renal Clear Cell Carcinoma 138 pTPM.
No cancer sample stained medium or high.
HPA PGF tissue · HPA PGF pathology · HPA protein class: FDA approved drug targets
RNA: tissue enriched (placenta 394 nTPM), detected in many normal tissues.
Medium: Cerebral cortex, Colon, Placenta, Smooth muscle, Testis.
RNA cancer enhanced: Kidney Renal Clear Cell Carcinoma 123 pTPM.
No cancer stained high; medium in breast cancer, head and neck cancer, melanoma, ovarian cancer.
HPA FLT1 tissue · HPA FLT1 pathology · HPA protein class: FDA approved drug targets
RNA: low tissue specificity, detected in many normal tissues. Blood: lineage enriched (T-cells 4 nTPM).
Medium: Breast, Cerebral cortex, Cervix, Colon, Duodenum, Epididymis, Esophagus, Fallopian tube.
RNA cancer enhanced: Kidney Renal Clear Cell Carcinoma 21 pTPM.
Medium only: breast cancer, carcinoid, colorectal cancer, endometrial cancer.
HPA FLT4 tissue · HPA FLT4 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| 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.
AI-081 is an experimental bispecific antibody from OncoC4 in phase 2 trials, aimed at PD-1 and VEGF / VEGFR.
Anlotinib is one of the most used cancer pills in China, first approved for lung cancer after other treatments have failed and then for several rarer tumours.
Axitinib is a selective VEGF-receptor pill, now given mainly with pembrolizumab or avelumab as first-line kidney cancer treatment.
Bevacizumab is a humanised antibody that soaks up VEGF-A, the signal tumours use to grow new blood vessels. Approved in 2004, it partners chemotherapy in colorectal, ovarian, cervical, lung, kidney and liver cancer and glioblastoma, and adds to trifluridine/tipiracil in late-line bowel cancer; hypertension, protein in the urine and bleeding are its characteristic side effects.
A blood-vessel-blocking antibody that shrinks glioblastoma on scans and reduces swelling, but has never been shown to help patients live longer.
A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.
A Chinese immunotherapy-plus-anti-angiogenic pill combination that clearly beat sorafenib in liver cancer, yet remains unapproved in the US after three manufacturing-related rejections.
Cediranib is a tablet that blocks the blood-vessel growth signal VEGF. In alveolar soft part sarcoma, a rare very vascular sarcoma that ignores chemotherapy, a randomised trial showed it shrinks tumours and delays progression, although it was never licensed.
Chiauranib is an experimental small-molecule drug from Chipscreen Biosciences in phase 3 trials for ovarian cancer, aimed at VEGF / VEGFR and KIT.
Donafenib is a Chinese redesign of sorafenib that lived longer than the original in a head-to-head liver cancer trial and is approved in China as a first-line option.
A Chinese-discovered pill that blocks the blood-vessel receptors, approved in 2023 for bowel cancer after all standard treatments.
A Chinese bispecific that beat Keytruda head-to-head on progression-free survival in lung cancer, the first drug ever to do so.
An oral anti-angiogenic pill that matched sorafenib in liver cancer with higher response rates, and partners with pembrolizumab in kidney and endometrial cancer.
Nintedanib is a triple angiokinase inhibitor pill (VEGFR, FGFR, PDGFR) approved for pulmonary fibrosis and, in the EU, for second-line lung adenocarcinoma with docetaxel. In mesothelioma the phase 2 part of LUME-Meso suggested slower progression in epithelioid disease, but the phase 3 part showed none, a much-cited warning about small randomised phase 2 signals.
Pazopanib is the only multi-kinase inhibitor approved for soft-tissue sarcoma (excluding fat-derived tumours), used after chemotherapy fails.
PM8002 is an experimental bispecific antibody from Biotheus in phase 3 trials for small-cell lung cancer, triple-negative breast cancer and neuroendocrine tumours, aimed at PD-L1 and VEGF / VEGFR.
Hemangeol is a liquid form of the blood-pressure drug propranolol approved to shrink infantile haemangiomas, the common benign blood-vessel tumours of babies, replacing steroids and surgery for most children who need treatment.
An antibody that blocks the VEGF receptor, approved in liver cancer only for patients with a high AFP blood level, the first biomarker-selected HCC drug.
A sorafenib successor that became the first second-line drug proven to prolong life in liver cancer (2017).
Apatinib, sold as rivoceranib outside China, was the first pill of its kind approved for stomach cancer and is now the partner of camrelizumab in first-line liver cancer.
The first drug ever to extend life in advanced liver cancer (2007), now mostly a comparator arm that newer combinations are measured against.
Sunitinib is an anti-angiogenic pill approved for pancreatic neuroendocrine tumours, kidney cancer and GIST.
Surufatinib is HUTCHMED's angio-immuno kinase inhibitor, approved in China in 2020 for non-pancreatic and in 2021 for pancreatic neuroendocrine tumours.
Tivozanib is a VEGF-receptor pill that hits VEGFR1 to 3 with little off-target kinase activity, so it is better tolerated than other anti-angiogenic pills, though hypertension and fatigue remain common. It is approved for kidney cancer after two or more prior treatments, and its TiNivo-2 trial showed that restarting immunotherapy after failure adds nothing.
Tovecimig is an experimental bispecific antibody from Compass Therapeutics in phase 3 trials for biliary tract cancer and bladder & urothelial cancer, aimed at VEGF / VEGFR.
Vandetanib was the first drug approved for medullary thyroid cancer (2011), now largely replaced by RET-selective selpercatinib.
Vorolanib is Betta Pharmaceuticals' oral VEGFR and PDGFR inhibitor, approved in China in 2023 with everolimus for advanced kidney cancer after a first kinase inhibitor has failed.
Zanzalintinib is an experimental small-molecule drug from Exelixis in phase 3 trials for neuroendocrine tumours, head and neck squamous cell carcinoma and renal cell carcinoma, aimed at VEGF / VEGFR and MET.
Ziv-aflibercept (Zaltrap) is a decoy receptor that soaks up the blood-vessel growth signal VEGF. It is added to the FOLFIRI chemotherapy combination for bowel cancer that has spread and progressed after oxaliplatin.
For the first time a new drug has beaten pembrolizumab, the global first-line standard, in a randomised lung cancer trial, and it did so by combining checkpoint blockade with anti-angiogenesis in one molecule. For patients outside China nothing changes yet: the drug is not approved in the West, the trial was single-country, and survival benefit has not been shown. If confirmed in the global HARMONi-3 and HARMONi-7 trials, PD-1 x VEGF bispecifics could replace PD-1 antibodies as the immunotherapy backbone.
A third refractory-line option, and the clearest example in colorectal cancer of a drug developed and approved in China going on to a global registration trial.
This is the paper Europe PMC returns for registry id NCT02394795 with the most citations, so it is the natural first reading for anyone following the PARADIGM trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
Trifluridine-tipiracil with bevacizumab is the refractory-line standard, and a reminder that combining two drugs already on the shelf can beat anything new in the same line.
Patients with newly diagnosed advanced clear-cell kidney cancer should receive an immunotherapy-based combination; lenvatinib plus pembrolizumab gives the highest response rate and longest PFS of the available options, at the cost of more side effects requiring dose adjustment. Sunitinib alone is no longer an appropriate standard. Choosing among the combinations depends on risk group, symptoms, comorbidity and the value placed on treatment-free survival, which favours nivolumab plus ipilimumab in intermediate and poor risk.
Patients with advanced liver cancer and good liver function should be offered atezolizumab plus bevacizumab (or durvalumab plus tremelimumab) rather than sorafenib as first treatment; median survival is now around 19 months and about a quarter of patients respond. Endoscopy to treat varices before starting bevacizumab is essential because of bleeding risk. Patients with poorer liver function (Child-Pugh B) or autoimmune disease or transplants were not studied.
It is the strongest evidence that the consensus subtypes could choose between the two first-line biologicals, and the clearest statement of why they have not: it is a retrospective analysis of a subset of one trial, on an assay nobody has validated for clinical use.
Women with newly diagnosed advanced ovarian cancer should have their tumour tested for BRCA mutations and homologous recombination deficiency, because those who are HRD-positive gain years of additional disease control and better survival from adding olaparib to bevacizumab maintenance. Those who are HRD-negative gain nothing from olaparib in this combination and should not be exposed to its toxicity and cost. HRD testing has become a routine part of ovarian cancer care as a result.
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.
Shares AI-081, Lenvatinib + pembrolizumab (pMMR endometrial cancer after platinum), Brian I. Rini, Nicoletta Colombo.
Shares HIF-1α (HIF1A), Hallmark: inducing or accessing vasculature, Angiogenesis, The pre-metastatic niche.
Shares RAISE, TRIBE2, VELOUR, Ziv-aflibercept.
Shares Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial, CALGB/SWOG 80405, FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3), CAIRO5.
Shares Chiauranib, Surufatinib, The pre-metastatic niche, Nutrient competition & metabolic immunosuppression.
Shares What actually holds T cells at the tumour border?, Immune exclusion, Bladder cancer (KEGG map), Renal cell carcinoma (KEGG map).
Shares Myeloid-derived suppressor cells (MDSCs), Ann-Lii Cheng, BEATcc / ENGOT-Cx10 / GOG-3030, Compass Therapeutics.
Shares Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial, Impact of consensus molecular subtype on survival in patients with metastatic colorectal cancer: results from CALGB/SWOG 80405, Alan P. Venook, Growth factor.