Inhibition of angiogenesis in the treatment of non‐small cell lung cancer

Abstract

Angiogenesis and its role in the growth and development of metastases has become a topic of increasing importance. In nonsmall cell lung cancer (NSCLC), vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, growth of the primary tumor, and development of metastases. In addition, elevated expression in tissue samples is a negative prognostic feature. For these reasons, VEGF is a worthy target for novel therapies. Recent clinical trials have shown that the anti-VEGF monoclonal antibody bevacizumab adds to the effect of chemotherapy in the metastatic setting. Hypertension and proteinuria are, as expected, commonly seen in this patient population, but the unexpected toxicity of lifethreatening hemoptysis has also been observed. This makes careful patient selection especially important for this class of drugs. Our understanding of the VEGF pathway is increasing, as are the number of available targeted agents. In addition to the monoclonal antibody, bevacizumab, VEGF receptor tyrosine kinase inhibitors, multitargeted kinase inhibitors, and combination VEGF and epidermal growth factor receptor (EGFR) inhibition, are all being evaluated in NSCLC. Small phase I and II trials have suggested modest benefit when used alone; however, we now know that the anti-angiogenic therapies work best in combination with chemotherapy. The results of ongoing trials using these agents in combination with standard therapy will provide more insight into their potential benefit. As it is known that small tumors require angiogenesis to grow and metastasize, the use of anti-angiogenic therapies in the adjuvant setting may provide even greater benefit, and increase the potential cure rate in this population of patients. The results of well-designed phase III trials will be required to truly understand how to best use this class of targeted therapies in resectable and metastatic NSCLC. (Cancer Sci 2007; 98: 1825-1830) N on-small cell lung cancer (NSCLC) remains the leading cause of cancer death in both men and women. In metastatic cases, prognosis remains poor and chemotherapy provides only minimal gains in overall survival. Response rates to combination chemotherapy regimens are approximately 19%, (1) and 1-year survival is less than 40%. There is an urgent need for novel therapies in the treatment of NSCLC. Even in surgically resectable cases, more than half of patients go on to develop metastatic disease in the next 5 years. Multiple chemotherapy combinations have been studied, and no particular regimen has provided a significant improvement in outcomes. As it seems we have reached the maximum benefit possible from standard chemotherapy, there is now an emphasis on targeted therapies. Angiogenesis and non-small cell lung cancer

Global Profiling and Molecular Characterization of Alternative Splicing Events Misregulated in Lung Cancer

“…Of the four lung adenocarcinoma-associated AS events identified in our study, only VEGFA transcripts with altered inclusion levels of exons 6 and/or 7 have been previously identified in NSCLC (26,59,62). VEGFs are important signaling proteins that promote de novo vascularization during development of the embryonic circulatory system and also stimulate blood vessel growth (angiogenesis) in tumor tissues.…”

Anti-angiogenic and Anti-metastatic Effects of .BETA.-1,3-D-Glucan Purified from Hanabiratake, Sparassis crispa

“…[16][17][18] Newly formed blood vessels help in tumor progression and promote metastatic spread of the tumor cells. Therefore, anti-angiogenic strategies are considered to be highly effective in cancer therapy.…”

“…Therefore, anti-angiogenic strategies are considered to be highly effective in cancer therapy. [16][17][18] In the present study, we elucidated the primary structure of SBG using methylation analysis, investigated the anti-angiogenic effects of SBG by using two different animal models, and further assessed the anti-metastatic activities in vivo. We further analyzed the possible mechanisms of SBG function by using human umbilical vein endothelial cells (HUVECs) in vitro.…”

“…[12][13][14][15] Vascular endothelial growth factor (VEGF) is the most prominent angiogenic protein often secreted by the solid tumor cells especially under hypoxic conditions. [16][17][18] Newly formed blood vessels help in tumor progression and promote metastatic spread of the tumor cells. Therefore, anti-angiogenic strategies are considered to be highly effective in cancer therapy.…”

1H,13C and 19F NMR data of N‐substituted 6‐(4‐methoxyphenyl)‐7H‐pyrrolo[2,3‐d]pyrimidin‐4‐amines in DMSO‐d6

“…[1] This is a large family of receptors including the epidermal growth factor receptor (EGFR) [2,3] and the vascular endothelial growth factor receptor among others. [4] Pyrrolopyrimidines have shown promising properties as TK inhibitors. [5 -8] Further, there is evidence that such compounds or analogues have prospects of becoming efficient antiprotozoal agents.…”