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- Title
Relevance of insulin-like growth factor 1 receptor gene expression as a prognostic factor in non-small-cell lung cancer.
- Authors
Agulló-Ortuño, M.; Díaz-García, C.; Agudo-López, Alba; Pérez, Carlos; Cortijo, Ana; Paz-Ares, Luis; López-Ríos, Fernando; Pozo, Francisco; de Castro, Javier; Cortés-Funes, Hernán; López Martín, José
- Abstract
Purpose: 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.
- Subjects
SOMATOMEDIN C; GENE expression; CELL receptors; NON-small-cell lung carcinoma; CELLULAR signal transduction; CARCINOGENESIS; PROGNOSIS
- Publication
Journal of Cancer Research & Clinical Oncology, 2015, Vol 141, Issue 1, p43
- ISSN
0171-5216
- Publication type
Article
- DOI
10.1007/s00432-014-1787-z