VEGF / VEGFR
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
- 1 · What it is
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
- 2 · What goes wrong in cancer
VEGF is an endothelial growth factor that is also immunosuppressive in the tumour microenvironment.
- 3 · How drugs use it
16 products aim at VEGF / VEGFR: antibodies, bispecific antibodies and small molecules. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
Biology
VEGF is an endothelial growth factor that is also immunosuppressive in the tumour microenvironment.
- Tumour vasculature across solid tumours
How common it is, by cancer
| 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.
Axitinib is a selective VEGF-receptor pill, now given mainly with pembrolizumab or avelumab as first-line kidney cancer treatment.
The first drug to starve tumours of blood vessels. Approved in 2004 for bowel cancer, it remains a standard partner for chemotherapy in many cancers and is the add-on that makes late-line pills work better.
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.
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.
An anti-angiogenic pill that looked promising in mesothelioma in a small trial but failed in the large one.
Pazopanib is the only multi-kinase inhibitor approved for soft-tissue sarcoma (excluding fat-derived tumours), used after chemotherapy fails.
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).
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.
Tivozanib is a highly selective VEGF-receptor pill for kidney cancer after two or more prior treatments, notable for its tolerability and for a trial that closed the door on immunotherapy rechallenge.
Vandetanib was the first drug approved for medullary thyroid cancer (2011), now largely replaced by RET-selective selpercatinib.
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.
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.
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.
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetPD-1
Shares HARMONi-2, KEYNOTE-775 / Study 309, Lenvatinib + pembrolizumab (pMMR endometrial cancer after platinum), Camrelizumab + rivoceranib.
- TargetPD-L1
Shares IMbrave150, BEATcc / ENGOT-Cx10 / GOG-3030, Myeloid-derived suppressor cells (MDSCs), National Taiwan University Hospital.
- CompanyMerck & Co. (MSD)
Shares CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer, HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer, PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours, Thymoma and thymic carcinoma.
- TechnologySmall-molecule kinase inhibitors
Shares DECISION, SELECT, Vandetanib, Nintedanib.
- TargetHIF-2α
Shares Hallmark: inducing or accessing vasculature, Angiogenesis, The pre-metastatic niche, VHL / HIF oxygen sensing.
- PathwayPD-1 / PD-L1 immune checkpoint & T-cell activation
Shares Immune exclusion, What actually holds T cells at the tumour border?, Ivonescimab, The cancer-immunity cycle.
- TargetCSF1R
Shares The pre-metastatic niche, Nutrient competition & metabolic immunosuppression, Intravasation & circulating tumour cells, Myeloid suppression: TAMs, MDSCs & don't-eat-me signals.
- ProductCisplatin
Shares BEATcc / ENGOT-Cx10 / GOG-3030, Thymoma and thymic carcinoma, Adrenocortical carcinoma, Nasopharyngeal carcinoma.