Novel targeted therapies in adrenocortical carcinoma.
Adrenocortical carcinoma is a rare cancer, but one that carries a poor prognosis due to its aggressive nature and unresponsiveness to conventional chemotherapeutic strategies. Over the past 12 years, there has been renewed interest in developing new therapies for this cancer, including identifying key signaling nodes responsible for cell proliferation.



Clinical trials of tyrosine kinase inhibitors as monotherapy have generally been disappointing, although the identification of exceptional responders may lead to the identification of targeted therapies that may produce responses in subsets of patients. Agents targeted to the Wnt signaling pathway, a known player in adrenal carcinogenesis, have been developed, although they have not yet been used specifically for adrenal cancer. There is current excitement about inhibitors of acetyl-coA cholesterol acetyl transferase 1, an enzyme required for intracellular cholesterol handling, although trials are still underway. Tools to target other proteins such as Steroidogenic Factor 1 and mechanistic target of rapamycin have been developed and are moving towards clinical application.



Progress is being made in the fight against adrenocortical carcinoma with the identification of new therapeutic targets and new means by which to attack them. Continued improvement in the prognosis for patients with adrenal cancer is expected as this research continues.
aDivision of OncologybDivision of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio, USA.
Bhavana
B
Konda
Lawrence S
LS
Kirschner
D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy*; D018268:Adrenocortical Carcinoma / Q000188:drug therapy*; D006801:Humans