Journal Article

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

Fukuoka, Hidenori

2015

Overview

Background 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. Methods In this review, a literature search were performed using PubMed with following terms; Cushing’s disease, EGFR, CDKs, cell cycle, and targeted therapy. Conclusion Accumulating evidence demonstrates that EGFR and cyclin E-CDK2 may be promising targets for treating ACTHomas.

• Publisher: Springer US,Springer Nature B.V
• Subject: ACTH-Secreting Pituitary Adenoma - complications / ACTH-Secreting Pituitary Adenoma - diagnosis / ACTH-Secreting Pituitary Adenoma - drug therapy / ACTH-Secreting Pituitary Adenoma - enzymology / Adenoma - complications / Adenoma - diagnosis / Adenoma - drug therapy / Adenoma - enzymology / Animals / Antineoplastic Agents - therapeutic use / Cushing Syndrome - diagnosis / Cushing Syndrome - drug therapy / Cushing Syndrome - enzymology / Cushing Syndrome - etiology / Cyclin-Dependent Kinases - antagonists & inhibitors / Cyclin-Dependent Kinases - metabolism / Endocrinology / Human Physiology / Humans / Medicine / Medicine & Public Health / Molecular Targeted Therapy / Pituitary Gland - drug effects / Pituitary Gland - enzymology / Pituitary Gland - pathology / Protein Kinase Inhibitors - therapeutic use / Receptor, Epidermal Growth Factor - antagonists & inhibitors / Receptor, Epidermal Growth Factor - metabolism / Signal Transduction - drug effects / Treatment Outcome