title: Tyrosine kinase inhibitors with antiangiogenic properties for the treatment of non-small cell lung cancer.
abstract: BACKGROUND
  The 5-year survival rate in NSCLC remains < 15% in spite of new chemotherapeutic regimens and targeted therapies. Tyrosine kinase inhibitors (TKIs) with antiangiogenic properties show promise as a new therapeutic approach for NSCLC in recent studies.
  
  
  METHODS
  This article reviews significant preclinical and clinical studies related to TKI therapy. Many drugs that target tyrosine kinases involved in tumor angiogenesis have recently been developed. Results of preclinical experiments and clinical trials for NSCLC are quite promising. However, response rates are low and the duration of therapeutic response is short. Mechanisms of resistance may reduce the efficacy of TKI therapy, and biomarkers of response are needed to select patients who are more likely to benefit from the therapy. Studies in mice have shown that antiangiogenic TKIs may increase metastasis, although no clear clinical evidence supports these results.
  
  
  RESULTS
  An understanding of the mechanisms of action, clinical trial results, biomarkers of response, adverse effects and possible mechanisms of resistance associated with novel TKI therapy in NSCLC.
  
  
  CONCLUSIONS
  More preclinical and clinical research on the efficacy of TKIs in treating NSCLC is needed, but present results offer great hope for patients.
authors.affiliation: Center for Applied Medical Research (CIMA), Division of Oncology, University of Navarra, Pamplona, 31008, Spain.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nguewa
authors.forename: Alfonso
authors.initials: A
authors.lastname: Calvo
authors.forename: Soni Savai
authors.initials: SS
authors.lastname: Pullamsetti
authors.forename: Gamal Andre
authors.initials: GA
authors.lastname: Banat
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Savai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy*; D016503:Drug Delivery Systems; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors