Biology and therapeutic targeting of IGF1R

Insuline-like Growth Factor (IGF) and IGF1 receptor (IGF1R) pathway is physiologically essential, with a cell trophic and hormonal role, inducing cell proliferation, migration and survival. In solid tumors, an elevated rate of free IGH may be correlated with a more important risk of lung cancer. Development of new molecules targeting this pathway is so predominant, with use of monoclonal anti-IGF1R antibody or IGF1R tyrosine kinase inhibitor. These molecules are all well tolerated, inducing predominantly a moderated hyperglycemia or fatigue. CP 751, 871 (figitumumab) is a monoclonal anti-IGF1R antibody, used in phase I and II for non small cell lung cancer (NSCLC), with promising results. In metastatic stages, almost 78 % of tumoral response rate was obtained in squamous cell carcinoma in association with carboplatin and paclitaxel. These results could be explained by an over-expression of IGF1R in squamous cell carcinoma, comparing to other histologies, that could be linked with a better response to figitumumab. A tot of phase III, concerning squamous cell carcinoma but also other histologies, are opening to validate these promising results on larger populations. (C) 2009 Elsevier Masson SAS. All rights reserved.