title: Relevance of insulin-like growth factor 1 receptor gene expression as a prognostic factor in non-small-cell lung cancer.
abstract: OBJECTIVE
  Signalling through the insulin-like growth factor 1 receptor (IGF-1R) is implicated in carcinogenesis, metastasis, and resistance to cytotoxic cancer therapies. The purpose of this study was to investigate the prognostic role of IGF-1R expression in surgically resected non-small-cell lung cancer (NSCLC), and responses to IGF-1R tyrosine kinase inhibitor NVP-ADW742 in a panel of lung cancer cell lines.
  
  
  METHODS
  Insulin-like growth factor 1 receptor (IGF-1R) expression was evaluated by quantitative RT-PCR in 115 NSCLC samples and in a panel of 6 NSCLC cell lines. Cytotoxicity experiments with IGF-1R inhibitor and conventional systemic drugs such as paclitaxel in cell lines were realised.
  
  
  RESULTS
  Insulin-like growth factor 1 receptor (IGF-1R) was differentially expressed across histologic subtypes, with the lowest levels observed in squamous cell tumours. Median survival was longer in patients with squamous tumour histology expressing low IGF-1R levels. In multivariable analysis, ageing and high tumour stage were significant predictors of worse overall survival. The hazard of death was lower in patients with squamous histology and low IGF-1R gene expression. There was no correlation between IGF-1R expression and response to tyrosine kinase inhibitor in cell lines tested. However, combination drug treatment resulted in synergistically enhanced antiproliferative effects on several cell lines.
  
  
  CONCLUSIONS
  These findings suggest that IGF-1R is a potential target for therapy in NSCLC patients. Combination therapies will have an important role in treatment.
authors.affiliation: Translational Oncology, Instituto de Investigación Hospital 12 de Octubre (i+12), Avda de Córdoba S/N, 28041, Madrid, Spain.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Agulló-Ortuño
authors.forename: C Vanesa
authors.initials: CV
authors.lastname: Díaz-García
authors.forename: Alba
authors.initials: A
authors.lastname: Agudo-López
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez
authors.forename: Ana
authors.initials: A
authors.lastname: Cortijo
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Fernando
authors.initials: F
authors.lastname: López-Ríos
authors.forename: Francisco
authors.initials: F
authors.lastname: Pozo
authors.forename: Javier
authors.initials: J
authors.lastname: de Castro
authors.forename: Hernán
authors.initials: H
authors.lastname: Cortés-Funes
authors.forename: José A
authors.initials: JA
authors.lastname: López Martín
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1
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