Journal
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 141, Issue 1, Pages 43-53Publisher
SPRINGER
DOI: 10.1007/s00432-014-1787-z
Keywords
Non-small-cell lung cancer; Insulin-like growth factor 1 receptor; Prognosis; Molecular markers
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Funding
- Fundacion Medica Mutua Madrilena (Madrid, Spain) [2008/107]
- Instituto de Salud Carlos III [FIS CM 06/00231]
- Spanish Association Against Cancer (AECC, PAO)
- Fundacion Mutua Madrilena, Spain [2010/0018]
- RTICC (Red Tematica de Investigacion Cooperativa de Cancer, ISCIII, Spain)
- Ministerio de Sanidad y Politica Social
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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. 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. 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. These findings suggest that IGF-1R is a potential target for therapy in NSCLC patients. Combination therapies will have an important role in treatment.
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