Bridging the Scientific Gaps to Identify Effective Treatments in Adrenocortical Cancer

SIMPLE SUMMARY: Adrenocortical cancer (ACC) is a rare malignancy with a poor prognosis and few treatment options. Surgery is the only curative option, but many patients present after the disease has become metastatic or recurs after surgery. There have been few advances in treatment since mitotane’s discovery in the 1960s, and it remains the only FDA-approved ACC treatment. This paper reviews the current treatment approaches, what we have recently learned about the disease, and the next steps needed to advance research and improve therapeutic options for this disease. ABSTRACT: Adrenocortical cancer (ACC) typically presents in advanced stages of disease and has a dismal prognosis. One of the foremost reasons for this is the lack of available systemic therapies, with mitotane remaining the backbone of treatment since its discovery in the 1960s, despite underwhelming efficacy. Surgery remains the only potentially curative option, but about half of patients will recur post-operatively, often with metastatic disease. Other local treatment options have been attempted but are only used practically on a case-by-case basis. Over the past few decades there have been significant advances in understanding the molecular background of ACC, but this has not yet translated to better treatment options. Attempts at novel treatment strategies have not provided significant clinical benefit. This paper reviews our current treatment options and molecular understanding of ACC and the reasons why a successful treatment has remained elusive. Additionally, we discuss the knowledge gaps that need to be overcome to bring us closer to successful treatment and ways to bridge them.