title: Understanding the Key to Targeting the IGF Axis in Cancer: A Biomarker Assessment.
abstract: Type 1 insulin like growth factor receptor (IGF-1R) targeted therapies showed compelling pre-clinical evidence; however, to date, this has failed to translate into patient benefit in Phase 2/3 trials in unselected patients. This was further complicated by the toxicity, including hyperglycemia, which largely results from the overlap between IGF and insulin signaling systems and associated feedback mechanisms. This has halted the clinical development of inhibitors targeting IGF signaling, which has limited the availability of biopsy samples for correlative studies to understand biomarkers of response. Indeed, a major factor contributing to lack of clinical benefit of IGF targeting agents has been difficulty in identifying patients with tumors driven by IGF signaling due to the lack of predictive biomarkers. In this review, we will describe the IGF system, rationale for targeting IGF signaling, the potential liabilities of targeting strategies, and potential biomarkers that may improve success.
authors.affiliation: Department of Oncology, Mayo Clinic , Rochester, MN , USA.
authors.forename: Kunal Amratlal
authors.initials: KA
authors.lastname: Lodhia
authors.affiliation: Department of Oncology, Mayo Clinic , Rochester, MN , USA.
authors.forename: Piyawan
authors.initials: P
authors.lastname: Tienchaiananda
authors.affiliation: Department of Oncology, Mayo Clinic , Rochester, MN , USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Haluska
keywords: IGF binding proteins; IGF system and signaling; biomarker discovery; endocrine system diseases; insulin receptor; insulin receptor substrate proteins; insulin-like growth factor receptor; targeted therapies