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[摘要]：Ganitumab (AMG-479) is a fully human monoclonal IgG(1) antibody that binds insulin-like growth factor 1 receptor (ICE-I receptor) and is being evaluated in clinical studies as monotherapy and in combination with other agents. The IGF system ganitumab targets has been implicated in the risk of cancer in recent years, including evidence from epidemiological data, research in cancer models and knowledge of the downstream signaling pathways Ras/Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and lipid kinase phosphatidylinositol 3-kinase (PI3K)/AKT, networks which are involved in cell proliferation and survival. As a result, various means of targeting the IGF-I receptor are being explored. Inhibition of ICE-I receptor activation by ganitumab has demonstrated oncolytic potential in vitro and in vivo, and the antibody has reached phase I clinical assessment in non-Hodgkin's lymphoma, phase I/II development for solid tumors, metastatic pancreatic cancer and small cell lung cancer, and phase II evaluation for soft tissue sarcoma, Ewing's sarcoma, neuroendocrine, ovarian, metastatic colorectal and breast cancer A phase Ill study of the combination of ganitumab and gemcitabine in metastatic adenocarcinoma of the pancreas is under way, and numerous other trials of ganitumab alone or in combination with other therapies are presently ongoing. |
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