139 BAY 57-9352: an inhibitor of VEGFR-2 and PDGFR receptor tyrosine kinases that demonstrates anti-angiogenic activity in vitro and in vivo

Abstract

It is thought that different families of angiogenic factors stimulate angiogenesis at different stages of tumor development. Our aim was to study whether the prognostic impact of vascular endothelial growth factors (VEGFs) and receptors (VEGFRs), platelet-derived growth factors (PDGFs) and receptors (PDGFRs) and fibroblast growth factor-2 (FGF-2) were associated with tumor size in non–small-cell lung cancer (NSCLC).Tumor tissue samples were obtained from 335 patients who had undergone resection for stage I-IIIA NSCLC, and tissue microarrays (TMAs) were constructed. Immunohistochemical techniques were used to evaluate the expression of VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, PDGF-A, PDGF-B, PDGFR-α, PDGFR-β, and FGF-2. Tumor size was categorized using the same cutoffs as in the 7th TNM classification for lung cancer.In multivariate analysis, high VEGFR-2 (HR, 1.87, [95% CI, 1.02-3.45]; P = .043), VEGFR-3 (HR, 2.18 [95% CI, 1.28-3.71]; P = .004) and the combination of high VEGF-A and high VEGFR-2 expression (low/low vs. high/high; HR, 3.28 [95% CI, 1.47-7.31]; P = .004) were independent negative prognostic factors in T2a tumors. High PDGF-B expression (HR, 11.72 [95% CI, 3.07-44.76]; P < .001) was an independent prognostic factor in T2b tumors.The prognostic impact of angiogenic factors depend in part on tumor size. VEGF-A/VEGFR-2 and VEGFR-3 seem to have their main impact in T2a tumors, while PDGF-B is a strong and independent prognostic factor in T2b tumors.