title: Clinical development of insulin-like growth factor receptor--1 (IGF-1R) inhibitors: at the crossroad?
abstract: Insulin like growth factor receptor (IGF-1R) targeting became one of the most investigated areas in anticancer drug development during the last decade. Strategies aiming to block IGF-1R activity include monoclonal antibodies, tyrosine kinase inhibitors and anti-ligands antibodies. Initial enthusiasm quickly encountered challenges. Unfortunately the validation of the efficacy of IGF-1R targeted agents in large clinical trials failed, however anecdotal single agent activity was seen in early studies. Consequently, questions regarding the selection of right target population and the appropriate trial design are arising. Despite the plethora of clinical trials conducted no predictive biomarker has been validated so far and resistance mechanisms to IGF-1R inhibitors remain unclear. The other issue to be addressed is how to best combine IGF-1R inhibitors with other therapeutic approaches. This review highlights the most relevant clinical data emphasizing the main tumor types where IGF-1R inhibition showed potential interest. We also tried to extract based on clinical and translational data some candidate biomarkers that could help better to select patient population who potentially could benefit most from this therapeutic approach.
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, 121 Boulevard de Waterloo, 1000, Brussels, Belgium. andrea.gombos@bordet.be
authors.forename: Andrea
authors.initials: A
authors.lastname: Gombos
authors.forename: Otto
authors.initials: O
authors.lastname: Metzger-Filho
authors.forename: Lissandra
authors.initials: L
authors.lastname: Dal Lago
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada-Hussein
mesh_terms: D018268:Adrenocortical Carcinoma / Q000188:drug therapy / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017526:Receptor, IGF Type 1