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Insulin-like growth factor-I receptor (IGF-IR) plays an important role in cell growth and differentiation. Overexpression of IGF-IR leads to abnormal cell proliferation and malignant transformation. IGF-IR deficient cells are resistant to carcinogenic transformation. In addition to its role in cell proliferation, IGF-IR also plays an important role in tumor cell survival. Overexpressed IGF-IR protects cells from apoptosis induced by serum withdrawal, tumor necrosis factor, etoposide, or interleukin-3 withdrawal in vitro. Elevated plasma levels of IGF-I are associated with prostate, breast, lung, and colon cancer risk. IGF-II is often overexpressed in colorectal cancer, neuroblastoma, liver, adrenal cortex, and Wilms tumors. IGF-IR is a signaling receptor for IGF-I and IGF-II ligands and is also overexpressed in some human cancers. The expression of IGF-IR on many tumor cell types suggests that this anti-IGF-IR monoclonal antibody has the potential to treat many different types of cancer.
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