Abstract 1125: The insulin-like growth factor (IGF) axis is involved in normal prostate differentiation and downregulated in local prostate cancer

Introduction and Objectives: Clinical trials targeting the insulin-like growth factor 1 receptor (IGF1R) in different tumors, including breast cancer, colorectal cancer, leukemia (ALL, CML), non-small-cell lung cancer (NSCLC), ovarian cancer, pancreatic cancer, prostate cancer and sarcomas are underway. Encouraging data from phase II studies in NSCLC and sarcomas led to rapid development of phase-III studies. However, a phase-III study with an anti-IGF1R antibody combined with erlotinib in advanced NSCLC was terminated recently for safety reasons and lack of efficiency (ClinicalTrials.gov Identifier: NCT00673049). Have we possibly moved to early to clinical trials without entirely understanding the role of the IGF axis in normal and cancer development? The IGF1R is part of a tightly regulated molecular network named IGF axis. The IGF axis is implicated in tumor development and progression, but also exerts essential functions in normal tissues, including control of growth processes, tissue homeostasis, differentiation and metabolism. Methods: Here we analyzed the mRNA expression level of the all members of the IGF axis, including IGF1, IGF2, IGFBP1-IGFBP6, IGF1R, IGF2R and INSR in microdissected tissue specimens of local prostate cancer. We compared IGF expression levels in malignant and benign prostate areas in both, the epithelial and the stromal compartment. Furthermore we investigated whether IGF expression levels are changed during normal prostate differentiation and describe a novel cellular model for prostate differentiation. Results: We show that the IGF axis is not up- but downregulated in local prostate cancer, in both the epithelial and the stromal compartment. Using cellular models we demonstrate that the IGF axis is induced during normal prostate epithelial differentiation and confirm herewith that the IGF axis is required for tissue homeostasis and normal epithelial differentiation in the prostate. Conclusions: Our data confirm a pivotal role of the IGF axis during normal prostate differentiation, which may overcomes its pro-oncogenic effect in local prostate cancer. Treatments of local prostate cancer with IGF1R inhibitors cannot be advised based on these data. Source of Funding: COMET center Oncotyrol and Tyrolean Cancer Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res