VEGFA

Overview

VEGFA encodes vascular endothelial growth factor A, the principal driver of tumor angiogenesis. VEGFA focal amplification occurs in HCC, and VEGFA signaling is the central mechanism of action of multiple approved HCC systemic therapies. Anti-VEGF strategies are also investigated in nasopharyngeal carcinoma (NPC).

Alterations observed in the corpus

• High-level focal amplification in 5% of HCCs (range 1-8%; SNP-array, n=704 patients). PMID:24798001
• Anti-VEGF antibody bevacizumab + sintilimab achieved ORR 54.5% in platinum-refractory ICI-naive recurrent/metastatic NPC. PMID:24952746
• Recurrent focal amplification in 7% of gastric cancers (TCGA, CIN subtype); rationale for VEGFR-pathway inhibition (e.g., ramucirumab). PMID:25079317
• Cited in the context of mouse lymphatic-metastasis models of cutaneous squamous cell carcinoma (cSCC); not directly assayed in the 29-tumour targeted-sequencing cohort PMID:25589618
• Focal amplification in 1% of HCC cases; listed as FDA-targetable alteration in the druggable landscape of HCC. PMID:25822088
• Transcriptionally up-regulated (immunosuppressive/angiogenic cytokine) in pre-treatment non-responding melanoma (SKCM) tumors; co-enriched within the IPRES innate anti-PD-1 resistance transcriptional signature; linked to a published mouse model of innate anti-PD-1 resistance (Peng et al. 2015) PMID:26997480.
• Amplified in esophageal adenocarcinoma (EAC); VEGFA amplification more common in EAC than CIN gastric adenocarcinoma in the TCGA integrated esophageal/GEA analysis; co-amplified alongside MYC in EAC PMID:28052061

Cancer types (linked)

• HCC — VEGFA amplification in 5%; angiogenic signaling prominent across all HCC subclasses; mechanistic target of sorafenib, lenvatinib, regorafenib, cabozantinib, ramucirumab, and bevacizumab. PMID:24798001
• NPC — VEGFA pathway targeted via bevacizumab (ORR 54.5% combined with sintilimab) and VEGFR2 TKI apatinib + camrelizumab (ORR 65.5%) in R/M disease. PMID:24952746
• SKCM — VEGFA up-regulation in non-responding pre-treatment tumors as part of IPRES; linked to innate anti-PD-1 resistance PMID:26997480.

Co-occurrence and mutual exclusivity

• No co-occurrence or mutual exclusivity data with specific partner genes reported in the current corpus.

Therapeutic relevance

• HCC: Sorafenib, lenvatinib, regorafenib, cabozantinib (multi-kinase VEGFR inhibitors); ramucirumab (anti-VEGFR2); bevacizumab + atezolizumab (FDA breakthrough designation). PMID:24798001
• NPC: Bevacizumab + sintilimab (ORR 54.5%); apatinib + camrelizumab (ORR 65.5%). PMID:24952746

Open questions

• No predictive biomarkers for VEGFA-targeting therapies have been validated in HCC; VEGFA amplification has not been prospectively validated as a predictive biomarker for anti-angiogenic agents.

Sources

• PMID:24798001
• PMID:24952746

This page was processed by crosslinker on 2026-05-14. - PMID:25079317

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:25822088 - PMID:26997480

• PMID:28052061

This page was processed by entity-page-writer on 2026-05-15.