Targeting Neovasculature with Multitargeted Antiangiogenesis Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer.
Chemotherapy has reached a plateau in the efforts for survival improvement in non-small cell lung cancer (NSCLC). The growing knowledge of NSCLC molecular pathobiology has led to the development of new treatments that target specific tumor functions. Angiogenesis is a tumor function leading to the formation of new tumor vessels that are crucial for its survival. Although vascular endothelial growth factor (VEGF) plays a primary role in angiogenesis, the inhibition of the VEGF pathway with VEGF-receptor (VEGFR) tyrosine kinase inhibitors (TKIs) is associated with a modest survival benefit due to the development of resistance by the tumor that has been mainly attributed to the up-regulation of other stimulators of angiogenesis. Thus, the use of multitargeted antiangiogenesis TKIs (MATKIs) for simultaneous inhibition of multiple angiogenic pathways has been proposed. This review summarizes data about novel treatment strategies incorporating the inhibition of angiogenesis with MATKIs in NSCLC. The data from all relevant studies shows that MATKIs do not offer additional survival benefit to currently available chemotherapeutic options in unselected NSCLC patients. However, the diversity in disease response to MATKI-containing regimens implies that specific patient subgroups may benefit from or be harmed by these agents. In this context, most studies agree that the VEGFR-targeting MATKIs are harmful in squamous NSCLC while specific MATKIs (i.e., motesanib, vandetanib and nintedanib) are associated with improved progression free survival in non-squamous NSCLC. However, overall survival benefit was found only in adenocarcinoma and Asian non-squamous NSCLC patients with the use of nintedanib and motesanib, respectively.
Oncology Unit, 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, 152 Μesogeion Avenue, 11527, Athens, Greece. vskouras@otenet.gr.|Department of Pulmonary Medicine, 401 General Army Hospital, 1 Kanellopoulou Avenue, 11526, Athens, Greece. vskouras@otenet.gr.
Vasileios S
http://orcid.org/0000-0002-7362-547X
VS
Skouras
Oncology Unit, 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, 152 Μesogeion Avenue, 11527, Athens, Greece.
Charis
C
Maragkos
Oncology Unit, 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, 152 Μesogeion Avenue, 11527, Athens, Greece.
Dimitra
D
Grapsa
Oncology Unit, 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, 152 Μesogeion Avenue, 11527, Athens, Greece.
Konstantinos N
KN
Syrigos
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017479:Receptors, Platelet-Derived Growth Factor