title: Minireview: Were the IGF Signaling Inhibitors All Bad?
abstract: Preclinical studies in the 1980s defined a role for IGF signaling in the development and sustainability of the malignant process. Subsequently, antibody, tyrosine kinase, and ligand inhibitors of the IGF receptor were manufactured. In the past decade, numerous clinical trials have tested the efficacy of IGF receptor inhibitors in the treatment of advanced tumors. Early-phase trials in heavily pretreated populations showed promise with complete or partial responses in a few patients and stable disease in many more. Unfortunately, the results of the early-phase trials did not pan out to later-phase trials. The lack of use of biomarkers to define subsets of patients that may benefit from IGF receptor blockade and compensatory signaling via other growth factor receptors such as the insulin, GH, and epidermal growth factor receptors may have played a role in the lack of efficacy of IGF receptor inhibition in phase III trials. Although these trials failed to show benefit, the trials have revealed previously unknown knowledge regarding the complex nature of IGF signaling. The knowledge obtained from these trials will be useful in designing future trials studying inhibitors of growth factor signaling.
authors.affiliation: Departments of Medicine (H.B., D.Y.) and Pharmacology (D.Y.) and Masonic Cancer Center (D.Y.), University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Heather
authors.initials: H
authors.lastname: Beckwith
authors.affiliation: Departments of Medicine (H.B., D.Y.) and Pharmacology (D.Y.) and Masonic Cancer Center (D.Y.), University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Douglas
authors.initials: D
authors.lastname: Yee
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C583557:IGF1 protein, human; C000597236:IGF1R protein, human; D047428:Protein Kinase Inhibitors; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; C569480:dalotuzumab; C545764:ganitumab; D017526:Receptor, IGF Type 1; C525021:figitumumab