IGF-1R is a receptor tyrosine kinase that is widely expressed in human epithelial cancers. The receptor is activated by its cognate ligands, insulin-like growth factor-I (IGF-I) and II (IGF-II). IGF binding activates intrinsic tyrosine kinase activity, resulting in receptor autophosphorylation and stimulation of signaling cascades that include the IRS-1/PI-3K/AKT/mTOR, and Grb2/Sos/Ras/MAPK pathways. In tumors, such as colorectal, NSCLC, and ovarian cancers, which may drive their own growth and survival through over-expression of autocrine IGF-II, the role of IGF-1R is especially critical. Epidemiological studies implicate the expression of IGF-1 in prostate, breast and colorectal cancer development. Hence, IGF-1R represents an important therapeutic target for the treatment of cancer. A novel small molecule IGF-1R kinase inhibitor (OSI-906) was discovered and developed at OSI and is currently in Phase I clinical trials. OSI-906 is expected to potentiate the antitumor activity of other MTT’s such as the EGFR tyrosine kinase inhibitor erlotinib against a broad range of tumor types.
References
- Larsson O et al. Role of insulin-like growth factor receptor signaling in cancer. Br J Cancer 2005; 92:2097-2101
- Samani AA et al. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007; 28(1): 20-47