New potential targets for treatment of Cushing's disease: epithelial growth factor receptor and cyclin-dependent kinases.

Abstract

Cushing's disease (CD) is caused by adrenocorticotropic hormone (ACTH)-producing pituitary adenomas (ACTHomas). Drug treatment for CD consists of three strategies: pituitary tumor-targeted therapy, steroidogenesis inhibitors, and glucocorticoid receptor antagonists. All of these strategies are under development, and several new drugs have recently been approved for clinical use or are being tested in clinical trials. Pituitary-targeted drugs are a particularly important method in the treatment of CD. Available pituitary tumor-targeted drugs include a dopamine receptor agonist and a somatostatin analog. Since disrupted cell cycle signaling is clearly associated with pathogenesis of ACTHomas which express active forms of epithelial growth factor receptor (EGFR), cyclins, and the catalytic subunit of cyclin-dependent kinases (CDKs), we focused on these molecules as therapeutic targets for ACTHomas. In this review, a literature search were performed using PubMed with following terms; Cushing's disease, EGFR, CDKs, cell cycle, and targeted therapy. Accumulating evidence demonstrates that EGFR and cyclin E-CDK2 may be promising targets for treating ACTHomas.