VEGFA

Overview

Vascular endothelial growth factor A (VEGFA) is a key signaling protein that plays a crucial role in angiogenesis, the process of new blood vessel formation from pre-existing vessels. It is part of the VEGF family, which includes several other growth factors that regulate vascular development and permeability. VEGFA primarily acts by binding to its receptors, VEGFR-1 and VEGFR-2, which are expressed on endothelial cells. This interaction stimulates endothelial cell proliferation, migration, and survival, thereby promoting the formation of new blood vessels. Due to its significant role in angiogenesis, VEGFA is a critical target in various therapeutic strategies, particularly in cancer treatment, where tumor growth and metastasis are often dependent on angiogenesis.

Focus of Latest Publications

Recent studies have explored diverse therapeutic strategies targeting VEGFA across multiple disease contexts. In retinal disease, neutralizing antibodies against VEGFA—including aflibercept, faricimab, and anti-VEGFA/ANG-2 bispecific antibodies—have demonstrated efficacy in suppressing pathological neovascularization and restoring endothelial barrier function in oxygen-induced retinopathy and neovascular age-related macular degeneration. Novel gene-editing approaches have also emerged, including CRISPR/Cas9 delivery via ionizable lipid nanoparticles designed to knockout the VEGFA gene itself, which reduced pathological neovascularization and retinal leakage in diabetic retinopathy models while maintaining biocompatibility. Beyond antibodies, receptor-based antagonism using VEGFR-1 decoy receptors (PB101) has been investigated for broader anti-angiogenic effects in gastric cancer by simultaneously inhibiting VEGF-A, VEGF-B, and PlGF. In cancer immunotherapy, bispecific antibodies simultaneously targeting VEGF-A and immune checkpoints—such as ivonescimab targeting PD-1/VEGF-A—have shown activity in metastatic cervical cancer and other solid tumors through combined angiogenic inhibition and immune checkpoint blockade.

In contrast, VEGFA promotion has been pursued for tissue regeneration and wound healing. Bioactive hydrogels co-delivering VEGFA and bFGF genes via nanoparticles combined with platelet-rich plasma have been designed to accelerate full-thickness skin wound healing. In neonatal hypoxic-ischemic brain injury, therapeutic magnetic nanovesicles enhanced endothelial survival and angiogenic repair through activation of the ITGB3/VEGFA signaling axis, promoting vascular recovery and neurological improvement. mesenchymal stem cell therapies promoting CD73 expression have been shown to upregulate VEGFA via hypoxia-inducible factor-1α-dependent pathways, enhancing angiogenesis and wound closure in diabetic pressure ulcer models.

VEGFA dysregulation has been identified as a driver of disease progression across multiple malignancies. In head and neck squamous cell carcinoma, hypoxia upregulates the MSC-AS1/ITGA5 axis, increasing VEGFA and PD-L1 expression and correlating with an immunosuppressive microenvironment. In diabetic retinopathy, lactate accumulation promotes HMGA1 lactylation at lysine 74, which enhances specificity protein 1–mediated VEGFA transcription and vascular dysfunction. In clear cell renal cell carcinoma, multi-omics analyses identified FLT1 as a central hub gene closely associated with VEGFA and Akt1, mediating epithelial-endothelial crosstalk that drives tumor progression; patients with high FLT1 expression were associated with poor immunotherapy responses. VEGFA expression has also been observed during cervical cancer progression and identified as a biomarker in hepatic neuroendocrine tumors, supporting its role as both a prognostic indicator and therapeutic target.

Emerging approaches combine VEGFA-targeting with complementary mechanisms to enhance therapeutic efficacy. In triple-negative breast cancer, fucoidan-modified nanoparticles targeting P-selectin suppress VEGF-A-mediated angiogenesis independently while simultaneously promoting M1 macrophage polarization. In renal cell carcinoma, integrative multi-target inhibitors (RING1) incorporating VEGF/Tie2-targeting modules self-assemble into nanonetworks that achieve prolonged tumor retention and enhanced vascular normalization alongside immune checkpoint blockade, demonstrating superior efficacy to conventional combination therapies. These findings collectively establish VEGFA as a critical nexus linking angiogenesis, immune regulation, and tissue homeostasis, with therapeutic strategies spanning antagonism for disease suppression and selective promotion for regenerative repair.

Key Publications

• NEWJul Aflibercept and Faricimab Equipotently Restore Endothelial Barrier Function. (Investigative ophthalmology & visual science, 2026, PMID 42390173): "To study the biological effects of aflibercept and faricimab on vascular endothelial growth factor (VEGF)-A165-induced vascular permeability in an in vitro head-to-head comparison using human-derived endothelial cells."
• NEWJul A hypoxia-responsive migrasome-related lncRNA signature predicts prognosis and suggests the MSC-AS1/ITGA5 axis as a potential therapeutic target in head and neck squamous cell carcinoma. (Functional & integrative genomics, 2026, PMID 42380675): "Hypoxia upregulated the MSC-AS1/ITGA5 axis and increased VEGFA/PD-L1 expression, along with changes in the migrasome-related protein TSPAN4, suggesting a potential association with migrasome-related molecular features, which requires direct experimental validation."
• Jun Targeted delivery of IDR-1018 via biomimetic magnetic nanovesicles suppresses neurovascular cell death and promotes angiogenic repair after neonatal hypoxic-ischemic brain injury. (Apoptosis : an international journal on programmed cell death, 2026, PMID 42228206): "...through activation of the ITGB3/VEGFA signaling axis."
• May A bioactive hydrogel integrating bFGF/VEGFA gene-loaded nanoparticles and platelet-rich plasma for accelerated full-thickness skin wound healing. (PloS one, 2026, PMID 42189841): "Here, we introduce a novel composite biomaterial: a hydrogel integrating nanoparticles loaded with basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) genes (bFGF/VEGFA NPs) with PRP (termed bFGF/VEGFA@PRP hydrogel), engineered to enable the synergistic delivery of growth factors and bioactive components."
• Jul HMGA1 Lactylation-Mediated Regulation of the SP1/VEGFA Axis in Pathological Angiogenesis Under Diabetic Retinopathy. (Diabetes, 2026, PMID 42102382): "The findings revealed that HMGA1 at lysine 74 (K74) directly promotes the transcriptional upregulation of specificity protein 1, enhancing vascular endothelial growth factor A expression and aggravating vascular dysfunction."
• May VEGFA-Targeted M3-F4 Ionizable Lipid Nanoparticles Improve Diabetic Retinopathy. (Molecular pharmaceutics, 2026, PMID 42089665): "Current therapies for DR primarily focus on inhibiting vascular endothelial growth factor A (VEGFA); however, their efficacy remains limited due to drug resistance and the requirement for repeated intravitreal injections."
• May Concurrent P-Selectin Targeting Nanoparticle Orchestrates Tumor-Immune Dynamics for Advanced Immunochemotherapy. (ACS nano, 2026, PMID 42047284): "Independent of targeting, fucoidan's bioactivity reduces cellular reactive oxygen species in cancer cells, promotes M1 macrophage polarization, and suppresses VEGF-A-mediated angiogenesis."
• May Therapeutic Efficacy of PB101 and Chemotherapy Combination in Preclinical Gastric Cancer Models. (Anticancer research, 2026, PMID 42049328): "Although anti-angiogenic therapies have yielded therapeutic benefit in GC, their efficacy is limited, as current vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-2 (VEGFR-2) targeted therapies eventually fail due to compensatory pathways involving VEGF-B and placental growth factor (PlGF)."
• May Obesity and Pro-Inflammatory Cytokines: Gene Expression Patterns Within Cervical Cancer Progression. (In vivo (Athens, Greece), 2026, PMID 42049436): "This study aimed to evaluate the gene expression levels of TNF-α, IL-6, IL-8, IL-10, and VEGF during CC progression in patients across different weight categories: normal weight, overweight, and obese."
• May New Pathological Insights into Biomarkers for Multimodal Therapeutic Approach in Hepatic Neuroendocrine Tumors: A Detailed Case Report. (In vivo (Athens, Greece), 2026, PMID 42049452): "Current biomarkers for neuroendocrine tumors including chromogranin A, synaptophysin, Ki-67, somatostatin receptors, mammalian target of rapamycin, vascular endothelial growth factor and its receptor, and O 6-methylguanine-DNA methyl transferase are important in diagnosis and treatment of NETs."