Abstract
Dr. Mark Mulvihill (OSI Pharmaceuticals) described the discovery and development of linsitinib (OSI-906), a potent and highly selective dual inhibitor of insulin-like growth factor 1 receptor (IGF-I receptor) and insulin receptor (IR) signaling, currently undergoing clinical evaluation in a number of cancers, including adrenocortical carcinoma (ACC) (1). IGF-I receptor, IR and IGF-I receptor/IR dimers are receptor tyrosine kinases (RTKs), which when activated on binding of their cognate ligands IGF-I, IGF-II and insulin, trigger critical signaling pathways involved in the etiology, progression and prognosis for a number of human cancers. Signaling through the IGF-I receptor has been linked to tumor cell proliferation and survival, as well as a key contributor toward tumor cells acquiring resistance to current anticancer therapeutics, including chemoand radiotherapies, as well as targeted small-molecule agents or antibodies. Although the IR signaling axis is still being unraveled, evidence has accumulated supporting a role in promoting tumor cell proliferation. Clinically, in both prostate and breast cancer patients, elevated
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