Chemotherapy for advanced adrenal cancer: improvement from a molecular approach?

What's known on the subject? and What does the study add? Adrenal cancer is classically a silent tumour that is often advanced at presentation. Conventional approaches to systemic therapy have been associated with relatively low objective tumour response rates, and modest survival benefit. More recent approaches have implemented targeted therapies focused on gene expression of these tumours, with some sustained remissions reported. This review assesses the utility of conventional and novel systematic therapies for adrenal carcinoma, and points the way to future implementation of molecular biology in the design and execution of clinical trails for advanced adrenal carcinoma. Advanced adrenal carcinoma remains a significant therapeutic challenge, with conventional approaches to systemic therapy having failed to achieve sustained objective remissions or major survival benefit in most instances. Several systemic therapies, including mitotane, suramin and gossypol, as well as cytotoxic agents, such as cisplatin and etoposide, have produced responses of ≈15–30%, with median survival figures of ≈6–15 months, depending on case selection bias, with only <10% 5‐year survival rates. Recent preclinical and pathological studies have indicated a range of potential targets for drugs, including WNT/beta‐catenin, epidermal growth factor receptor, RAF and k‐RAS; similar applications in melanoma and renal carcinoma have achieved significant gains, and these targets are worthy of further, structured investigation. Advanced adrenal carcinoma constitutes an orphan disease, with a high mortality rate, and merits investment in clinical trials.