Vascular Endothelial Growth Factor A (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.

Recent Publications Summary

Recent publications demonstrate VEGFA's pivotal role across diverse therapeutic contexts, spanning tissue regeneration, cancer treatment, and ocular diseases. In tissue repair applications, VEGFA has been strategically activated to enhance healing outcomes. β-cell-targeted RNA activation of VEGF-A accelerated vascular integration during pancreatic islet transplantation, reducing metabolic compromise and autophagic stress while preserving endpoint vascular density 42547502Aug. Similarly, bioactive hydrogels integrating bFGF/VEGFA gene-loaded nanoparticles with platelet-rich plasma demonstrated synergistic delivery of growth factors for full-thickness skin wound healing 42189841May. In diabetic wound healing, CD73-positive mesenchymal stem cells promoted angiogenesis through the HIF-1α/VEGF pathway, with VEGFA expression modulation under hypoxic conditions contributing to accelerated wound closure 41819469Mar. A botanical approach utilizing Platycladus orientalis leaf extract promoted dermal papilla cell proliferation and angiogenesis via activation of the VEGFA/Bcl-2 signaling pathway for androgenetic alopecia treatment 42469978Jul. Additionally, targeted delivery of the host defense peptide IDR-1018 via biomimetic magnetic nanovesicles enhanced endothelial survival through activation of the ITGB3/VEGFA signaling axis in neonatal hypoxic-ischemic brain injury 42228206Jun.

In contrast, VEGFA inhibition has emerged as a central strategy for treating angiogenesis-dependent diseases. VEGFA-targeting CRISPR/Cas9 genome editing using optimized ionizable lipid nanoparticles (M3-F4 LNP) achieved VEGFA knockout in retinal microvascular endothelial cells, offering a novel approach to diabetic retinopathy 42089665May. Molecular investigations revealed that HMGA1 lactylation promotes transcriptional upregulation of VEGFA in diabetic retinopathy through the SP1 axis, identifying a posttranslational modification target for therapeutic intervention 42102382May. Multiple monoclonal antibody strategies targeting VEGFA have been evaluated clinically: the bispecific antibody faricimab, which inhibits both VEGF-A and angiopoietin-2, showed rapid improvements in anatomical and functional outcomes in treatment-naïve neovascular age-related macular degeneration 42033608Apr42390173Jul. In neovascular retinal diseases, anti-VEGFA and anti-ANG-2 antibodies administered intraocularly suppressed pathological neovascularization in oxygen-induced retinopathy models, with bispecific antibodies demonstrating superior efficacy while reversing neuronal cell loss 41944819Apr.

VEGFA inhibition has also been explored across multiple cancer types as part of combination therapeutic strategies. The bispecific antibody ivonescimab, which simultaneously targets programmed death receptor-1 and VEGF-A, demonstrated robust anti-tumor activity in recurrent or metastatic cervical cancer, combining immunotherapy with anti-angiogenic effects 42012232Apr. A multitarget switchable CAR-T approach integrated anti-Her2 single-chain variable fragments with spliced VEGF-A (VEGF121) to simultaneously target Her2, VEGFR1, and VEGFR2, achieving superior tumor eradication and vasculature disruption compared with conventional CAR-T in syngeneic and xenograft models 42349416Jun. In gastric cancer, the VEGFR-1 decoy receptor PB101—which inhibits VEGF-A, VEGF-B, and placental growth factor—was evaluated to overcome compensatory anti-angiogenic pathways 42049328Apr. For renal cell carcinoma, the multi-target peptide inhibitor RING1 incorporated VEGF/Tie2-targeting modules to simultaneously induce vascular normalization and immune checkpoint blockade, achieving an 1.8-fold enhancement in vascular normalization compared to clinical combination therapy 41705472Feb. In kaposiform hemangioendotheliomas presenting with Kasabach-Merritt phenomenon, anti-VEGF inhibitors including bevacizumab were employed in refractory cases where conventional medical management failed 42033477Apr. Additionally, P-selectin-targeted nanoparticles suppressed VEGF-A-mediated angiogenesis while promoting M1 macrophage polarization in tumor immunochemotherapy 42047284Apr.

VEGFA has also been investigated as a drug target in the context of genetic and systemic associations. Genome-wide association and Mendelian randomization analyses identified VEGFA among seven triglyceride-lowering drug target genes relevant to endometriosis risk, with pathway enrichment analysis revealing involvement in blood vessel development and cell adhesion 42594068Aug. Gene expression studies during cervical cancer progression demonstrated dysregulation of VEGF across different patient weight categories, linking obesity-associated inflammation to VEGFA expression 42049436Apr. In clear cell renal cell carcinoma, comprehensive multi-omics analyses identified FLT1 as a pivotal gene closely associated with VEGFA in a senescence-driven network promoting ccRCC progression 41999263Apr. Bibliometric analysis of growth factor mechanisms in osteoarthritis confirmed VEGF as one of the most highly prevalent growth factors studied globally alongside TGF-β, IGF, and NGF, reflecting shifting research emphases toward multifactorial delivery platforms and CRISPR-based gene editing approaches 41890882Mar. Finally, VEGF and its receptor were identified as important biomarkers in neuroendocrine tumors, contributing to diagnosis and therapeutic decision-making in this heterogeneous cancer group 42049452Apr.

What Changes, What Holds

1. VEGFA activation accelerates healing across diverse tissue types
NEW DIRECTION Activation of VEGFA enhances vascular integration and healing rates in pancreatic islet transplantation, diabetic wounds, neonatal brain injury, and follicular regeneration 42547502Aug41819469Mar. Where the overview establishes VEGFA's role in angiogenesis generally and cancer-driven neovascularization, this work demonstrates therapeutic repurposing through intentional VEGFA upregulation for reparative outcomes. Modulation via HIF-1α/VEGF and VEGFA/Bcl-2 pathways reveals mechanistic targets for enhancing rather than blocking VEGFA signaling.

2. VEGFA suppression reverses pathological angiogenesis in ocular disease
NEW DIRECTION VEGFA inhibition extends beyond cancer to ocular pathology: bispecific antibodies targeting VEGF-A and angiopoietin-2 (faricimab) reverse neovascular AMD rapidly 42033608Apr42390173Jul, and CRISPR/Cas9-mediated VEGFA knockout addresses diabetic retinopathy 42089665May. HMGA1 lactylation emerges as an upstream transcriptional driver of VEGFA upregulation in retinal disease 42102382May. The overview positions VEGFA inhibition in cancer; these findings establish anti-VEGFA as disease-modifying for ischemic and inflammatory ocular pathology.

3. VEGFA inhibition combines with immunotherapy and engineered cell therapy in cancer
REINFORCES Multi-modal combinations now pair VEGFA blockade with checkpoint inhibition—bispecific anti-PD-1/VEGF-A (ivonescimab) in cervical cancer 42012232Apr, and engineered CAR-T cells co-targeting VEGF-A with superior tumor eradication 42349416Jun. Vascular normalization via multi-target VEGF/Tie2 inhibition enhances immune checkpoint efficacy in renal cancer 41705472Feb. These findings reinforce VEGFA's established role as a cancer target by demonstrating synergy with immune modulation and cellular therapy; combination efficacy validates rather than displaces the underlying mechanistic basis.

4. VEGFA links to endometriosis risk and serves as a biomarker in endocrine neoplasms
NEW DIRECTION Mendelian randomization identifies VEGFA among triglyceride-lowering drug targets associated with endometriosis risk 42594068Aug, suggesting metabolic-inflammatory mechanisms beyond classical angiogenesis. VEGFA dysregulation emerges as a diagnostic and prognostic biomarker in neuroendocrine tumors 42049452Apr, and FLT1-VEGFA co-expression drives senescence-dependent renal cancer progression 41999263Apr. The overview positions VEGFA in vascular biology and cancer growth; these findings reveal VEGFA as a polyvalent node in metabolic disease and endocrine oncology where dysregulation reflects systemic pathophysiology.

Overview update candidates: VEGFA activation for tissue regeneration (pancreatic islet and wound healing); VEGFA inhibition for ocular disease (diabetic retinopathy and neovascular AMD); and VEGFA as a biomarker in neuroendocrine tumors and endometriosis-linked metabolic disease.