Hsp90 Inhibitor Treatment for Cushing Syndrome and Other Diseases

Abstract

Hsp90 is a chaperone protein commonly involved with the proper folding of cellular protein products into mature proteins. The chaperone is under investigation for its role in abnormal cell propagation, particularly in cancerous cells. In Cushing syndrome, Hsp90 will tightly bind the glucocorticoid receptor protein and cause a decrease in receptor sensitivity. The inactivity of the receptor protein leads to corticotroph adenomas and the main symptoms of Cushing syndrome. Three Hsp90 inhibitors were tested in corticotroph adenomas in the treatment of Cushing syndrome symptoms. It was found that silibinin, a recently discovered Hsp90 inhibitor, upregulated the sensitivity of the glucocorticoid receptor and led to alleviation of symptoms in mice models. These results imply that Hsp90 inhibitors may be a viable answer to diseases beyond cancer.