title: Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: lessons from the first clinical trials.
abstract: The insulin-like growth factor-I receptor (IGF-IR) was first cloned in 1986. Since then, intense work has defined classic phosphorelays activated via the IGF-IR, which regulate cell proliferation, apoptosis, motility, and fate. The understanding of the roles of hormones in cancer and the growth hormone-IGF-IGF-binding protein axis specifically has yield to a second wave of development: the design of specific inhibitors that interrupt the signaling associated with this axis. The ability to manipulate these pathways holds not only significant therapeutic implications but also increase the chance of deeper insight about the role of the axis in carcinogenesis and metastasis. Nowadays, >25 molecules with the same goal are at different stages of development. Here, we review the clinical and preclinical experience with the two most-investigated strategies, tyrosine kinase inhibitors and monoclonal antibodies, and the advantages and disadvantages of each strategy, as well as other alternatives and possible drug combinations. We also review the biomarkers explored in the first clinical trials, the strategies that have been explored thus far, and the clinical trials that are going to explore their role in cancer treatment.
authors.affiliation: Investigational Cancer Therapeutics, University of Texas M. D. Anderson Cancer Center, Unit 455, 1515 Holcombe Boulevard, Houston, TX 77030, USA. jrodonahnert@gmail.com
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodon
authors.forename: Victoria
authors.initials: V
authors.lastname: DeSantos
authors.forename: Robert Jean
authors.initials: RJ
authors.lastname: Ferry
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017526:Receptor, IGF Type 1
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