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Cixutumumab
Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors.[1][2] This drug was developed by ImClone Systems, since acquired by Eli Lilly, using phage display technology from Dyax.[citation needed] It is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor (IGF-1R) with potential antineoplastic activity. Cixutumumab selectively binds to membrane-bound IGF-1R, thereby preventing the binding of the ligand IGF-1 and subsequent activation of PI3K/AKT signaling pathway. Downregulation of the PI3K/AKT survival pathway may result in the induction of cancer cell apoptosis and may decrease cancer cellular proliferation. IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily overexpressed by many cancer cell types, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.[3] ResearchPhase II clinical trials have been completed in patients with non-small cell lung cancer,[4][5][6] metastatic rhabdomyosarcoma,[7] metastatic prostate cancer,[8] metastatic pancreatic cancer,[9] metastatic esophageal cancer,[10] bone cancer,[11] sarcoma,[12] solid tumors,[13] ocular melanoma,[14] hepatocellular carcinoma,[15][16] breast cancer[17] and other forms of cancer. Despite these extensive trials, more than 45 phase I and II clinical trials in total, phase III trials have never been undertaken and Eli Lilly has removed cixutumumab from their development pipeline.[18] References
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