Gastric Cancer and Angiogenesis: Is VEGF a Useful Biomarker to Assess Progression and Remission?

Abstract

Gastric cancer (GC) has high mortality owing to its aggressive nature. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of GC. The aim of this work was to review the angiogenic biomarkers related to the behavior of GC, documented in the literature. A search of the PubMed database was conducted with the MeSH terms: “Stomach neoplasms/blood [MeSH] or stomach neoplasms/blood supply [MeSH] and angiogenic proteins/blood [Major]”. A total of 30 articles were initially collected, and 4 were subsequently excluded. Among the 26 articles collected, 16 examined the role of vascular endothelial growth factor (VEGF), 4 studied endostatin, 3 investigated angiopoietin (Ang)-2, 2 studied the Ang-like protein 2 (ANGTPL2), and 1 each examined interleukin (IL)-12, IL-8, and hypoxia inducible factor. Regarding VEGF, 6 articles concluded that the protein was related to lymph node metastasis or distant metastases. Five articles concluded that VEGF levels were elevated in the presence of GC and decreased following tumor regression, suggesting that VEGF levels could be a predictor of recurrence. Four articles concluded that high VEGF levels were correlated with poor prognosis and lower survival rates. Ang-2 and ANGTPL2 were elevated in GC and associated with more aggressive disease. Endostatin was associated with intestinal GC. VEGF is the most extensively studied angiogenic factor. It is associated with the presence of neoplastic disease and lymph node metastasis. It appears to be a good biomarker for disease progression and remission, but not for diagnosis. The data regarding other biomarkers are inconclusive.

Combination of apatinib and continuous nutritional support for a gastric cancer patient with brain metastasis prolongs survival

“…Apatinib (Hengrui Pharmaceutical Co., Ltd., Jiangsu, People’s Republic of China), a small molecule tyrosine kinase inhibitor, identifies VEGFR‐2 as a drug target and blocks VEGFR‐2‐induced angiogenic signalling to inhibit tumour‐induced angiogenesis, thereby preventing tumour growth . VEGF is closely associated with oedema, and anti‐VEGF therapy could normalize blood‐brain barrier function to treat brain oedema .…”

Efficacy of Combined VEGFR1-3, PDGFα/β, and FGFR1-3 Blockade Using Nintedanib for Esophagogastric Cancer

“…All tumors depend on angiogenesis for growth and metastatic progression, and increased VEGFR2 signaling is associated with poorer outcomes in gastric cancer (1,2). This rationale motivated trials of the VEGFR2-directed mAb, ramucirumab, in patients with metastatic esophagogastric cancer, which demonstrated improved progression-free (PFS) and overall survival (OS; refs.…”

Inhibiting the proliferation and metastasis of hilar cholangiocarcinoma cells by blocking the expression of vascular endothelial growth factor with small interfering RNA

“…There have been a number of studies evaluating VEGF in the treatment of tumors, including gastrointestinal cancer, liver cancer, mammary cancer, prostate cancer and pancreatic cancer (20)(21)(22)(23)(24). In addition to these studies, several anti-angiogenic drugs, including Bevacizumab and Celecoxib, have been developed and used in clinical practice (25,26).…”