Current status and perspective of angiogenesis and antivascular therapeutic strategy: non-small cell lung cancer

Abstract

Lung cancer is the leading cause of cancer death worldwide, and most patients die of metastatic disease. Angiogenesis, namely, neovascularization from preexisting vasculature, is necessary for tumor growth in both primary and distant organs to supply oxygen and nutrition. Angiogenesis consists of sprouting and nonsprouting (the enlargement, splitting, and fusion of preexisting vessels) processes, and both can occur concurrently. The growth of non-small cell lung cancer (NSCLC), which accounts for more than 80% of all lung cancers, is usually dependent on angiogenesis, which is regulated by complex mechanisms in the presence of various angiogenesis-related molecules. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is one of the most potent angiogenic molecules, while also regulating both angiogenesis and vascular permeability and hence promoting tumor progression and the development of malignant pleural effusions in NSCLC. Recent clinical trials showed that the anti-VEGF antibody bevacizumab, combined with standard first-line chemotherapy, provided a statistically and clinically significant survival advantage with tolerable toxicity. In addition, the combined use of the anti-VEGF antibody with an inhibitor of epidermal growth factor receptor (EGFR) has also shown favorable antitumor efficiency. These successes proved the validity of an antivasculature strategy for NSCLC. Furthermore, a large number of antivasculature agents have been shown to be effective against multiple targets. The efficiency of these compounds is currently being investigated in clinical trials for NSCLC.

Follistatin as an Inhibitor of Experimental Metastasis

“…In this tumor model, potentially due to the ablation of the natural killer cells, large numbers of hepatic and osteolytic metastatic lesions were observed. This confirms the prior study of bone metastasis by these tumors (21), supporting this as an exciting model for organ-specific metastasis studies.…”

Follistatin Suppresses the Production of Experimental Multiple-Organ Metastasis by Small Cell Lung Cancer Cells in Natural Killer Cell–Depleted SCID Mice

“…Angiogenesis is regulated by the balance of proangiogenic molecules, such as vascular endothelial growth factor, fibroblast growth factor-2, interleukin-8, and antiangiogenic molecules, such as thrombospondin-1, angiostatin, and endostatin (41). Whereas the roles of FST and activin in angiogenesis still remain controversial (42), several reports showed that activin induces the expression of vascular endothelial growth factor and that it controls tubulogenesis of endothelial cells (39,43,44).…”

Serum Angiopoietin-2 as a Clinical Marker for Lung Cancer

“…8,20 A correlation between the degree of angiogenesis and systemic metastasis has been reported in a variety of malignant tumors, including lung cancer. 22,34 Variable results have been reported concerning the prognostic implications of serum VEGF levels in lung cancer.…”

“…4 -6 Angiogenesis is controlled by the interplay of numerous positive and negative factors, 7 and proangiogenic factors include many growth factors, proteases, and cytokines. 8 Of these, vascular endothelial growth factor (VEGF) is the most extensively studied and is significantly related to tumor progression, metastasis, and prognosis. 9 -11 Angiopoietins play an important role in angiogenesis in concert with VEGF.…”