The VEGF pathway in lung cancer
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Review Article
The VEGF pathway in lung cancer Michalis Alevizakos · Serafim Kaltsas · Konstantinos N. Syrigos
Received: 26 June 2013 / Accepted: 13 September 2013 / Published online: 2 October 2013 © Springer-Verlag Berlin Heidelberg 2013
Abstract Introduction Lung cancer is a disease whose prognosis has remained poor in the last decades. Recent advances in the understanding of the molecular pathways behind this disease have revealed several mediators of important tumor functions. One of these functions is angiogenesis, which is considered essential for tumor growth and propagation, and a key mediator promoting this process is the vascular endothelial growth factor (VEGF). In lung cancer, VEGF plays a significant role in establishing a vascular supply within the tumor. Thus, a new class of drugs has emerged, targeting its pathway, which has offered substantial, albeit small, improvements in patient prognosis. Areas covered The VEGF pathway and its role in a multitude of different human cancers are presented at first. We then proceed by analyzing its importance in lung cancer and exploring the therapeutic benefits achieved by its targeting, which set new goals for the future. Expert opinion Today, the VEGF pathway remains an attractive target for anticancer treatment, and the way forward requires detection of predictive markers and efforts for a more complete angiogenic blockade. Keywords VEGF · Cancer · Lung · Angiogenesis · Carcinogenesis · Anti-angiogenic · Therapy
M. Alevizakos · S. Kaltsas · K. N. Syrigos (*) Oncology Unit GPP, Sotiria General Hospital, Athens School of Medicine, Athens, Greece e-mail: [email protected] K. N. Syrigos Yale School of Medicine, New Haven, CT, USA
Abbreviations VEGF Vascular and endothelial growth factor VEGFR Vascular and endothelial growth factor receptor MVD Mean vascular density NSCLC Non-small-cell lung carcinoma SCLC Small cell lung carcinoma ECM Extracellular matrix MMP Matrix metalloproteinase NP1 Neuropilin-1 HSPG Heparin sulfate proteoglycan FGF Fibroblast growth factor PDGF Platelet-derived growth factor HIF-1 Hypoxia-induced factor 1 pVHL Von Hippel–Lindau protein EGF Epidermal growth factor IGF-1 Insulin-like growth factor 1 TGF-a Transforming growth factor a TGF-b Transforming growth factor b IL-1 Interleukin-1 Il-6 Interleukin-6 PFS Progression-free survival RR Response rate OS Overall survival MT-TKI Multitarget tyrosine kinase inhibitor miRNA microRNA COX-2 Cyclooxygenase 2 PGE2 Prostaglandin E2 mAb Monoclonal antibody EGFR Epidermal growth factor receptor PGF Placental growth factor PDGFR Platelet-derived growth factor receptor ICAM-1 Intracellular adhesion molecule 1 IC50 Half maximal inhibitory concentration SNPs Single-nucleotide polymorphisms
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Introduction Any growing tissue, in order to survive and maintain its growth, needs adequate blood supply as a means of metabolic support and so do malignancies, the champions of aberrant, unneeded and uncontrolled growth. In the latter, that particular need is met vi
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