title: Motesanib and advanced NSCLC: experiences and expectations.
abstract: BACKGROUND
  Benefits from conventional chemotherapy in NSCLC have plateaued. Accordingly, sizeable efforts have gone into developing novel therapies. Tumor angiogenesis mediated principally by VEGF has emerged as an alluring target because of its vital role in tumor growth, sustenance and metastasis. The Eastern Cooperative Oncology Group (ECOG) trial E4599 showed significant improvement in overall survival with addition of bevacizumab, a VEGF monoclonal antibody, to cytotoxic chemotherapy in metastatic NSCLC. A number of compounds targeting tumor angiogenesis have since gone into preclinical and clinical testing. The multifaceted nature of cancer has led to development of multitarget tyrosine kinase inhibitors (MTKIs) that target several pathways concomitantly. Motesanib, an orally administered potent small molecule, targets VEGFR 1 - 3, PDGFR and KIT. Oral bioavailability and preliminary evidence of activity make this compound an appealing choice for additional investigations.
  
  
  METHODS
  This review summarizes the background of angiogenesis and rationale for targeting the VEGF pathway in NSCLC. The authors also review recent clinical trial data evaluating motesanib.
  
  
  CONCLUSIONS
  VEGF is a validated target in NSCLC. In early trials motesanib has shown promising activity in NSCLC with tolerable toxicity profile. A Phase III trial with motesanib in combination with chemotherapy is ongoing.
authors.affiliation: Hematology and Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Faculty Center (FC11.2049), Unit 0421, Houston, TX 77030, USA.
authors.forename: Kanwal Pratap Singh
authors.initials: KP
authors.lastname: Raghav
authors.forename: George R
authors.initials: GR
authors.lastname: Blumenschein
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001682:Biological Availability; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000503:physiopathology; D016503:Drug Delivery Systems; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D009841:Oligonucleotides; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D009841:Oligonucleotides; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; C519562:imetelstat