title: Targeted therapies for adrenocortical carcinoma: IGF and beyond.
abstract: Standard chemotherapy for adrenocortical cancer currently is under evaluation in the context of the recently completed FIRM-ACT evaluating the combination of mitotane with either streptozocin or etoposide, cisplatin, and doxorubicin. New agents are eagerly sought by the ACC community that hopes to make progress against this deadly disease. Investigators have begun to dissect the molecular and genomic context of ACC with a goal of identifying potential novel therapeutic agents. One gene consistently overexpressed in ACC is insulin growth factor type 2. Targeting its receptor IGF1R has shown encouraging results in ACC cell lines and against murine xenografts. As a result, clinical trials to evaluate agents targeting the IGF1R have been done including mitotane and IMC-A12 (a monoclonal antibody) and the GALACCTIC trial that has just completed accrual to evaluate OSI-906, a small molecule IGF1R antagonist. On the horizon are other agents targeting other tyrosine kinases, including EGF and FGF, and novel strategies such as individualized tumor analysis to select treatment.
authors.affiliation: Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Demeure
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Bussey
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kirschner
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008939:Mitotane / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D057285:Precision Medicine; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D054852:Small Molecule Libraries; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D054852:Small Molecule Libraries; C557414:cixutumumab; D007335:Insulin-Like Growth Factor II; D008939:Mitotane; D017526:Receptor, IGF Type 1