Relevance of insulin-like growth factor 1 receptor gene expression as a prognostic factor in non-small-cell lung cancer.

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.

• Authors: M Teresa Agulló-Ortuño, C Vanesa Díaz-García, Alba Agudo-López, Carlos Pérez, Ana Cortijo, Luis Paz-Ares, Fernando López-Ríos, Francisco Pozo, Javier de Castro, Hernán Cortés-Funes, José A López Martín
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 141 Issue 1 Pg. 43-53 (Jan 2015) ISSN: 1432-1335 [Electronic] Germany
• PMID: 25081930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• RNA, Messenger
• Receptor, IGF Type 1

Topics

• Adenocarcinoma (genetics, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Carcinoma, Large Cell (genetics, mortality, pathology)
• Carcinoma, Non-Small-Cell Lung (genetics, mortality, pathology)
• Carcinoma, Squamous Cell (genetics, mortality, pathology)
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (genetics, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Receptor, IGF Type 1 (genetics)
• Retrospective Studies
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate
• Tumor Cells, Cultured