Emerging drugs for the treatment of adrenocortical carcinoma

ABSTRACT

Introduction: Adrenocortical cancer (ACC) is a rare and aggressive disease with a median survival of 14–17 months and 5-year survival of around 20% for advanced disease. Emerging evidence of sub-groups of ACC with specific molecular drivers indicate ACC may be amenable to inhibition of receptor tyrosine kinases involved in growth and angiogenic signaling. A significant subset of patients may also be responsive to immune strategies.

Areas covered: This review outlines approaches of targeting upregulated growth pathways including Insulin-like Growth Factor, Vascular Endothelial Growth Factor, Fibroblast Growth Factor and Epidermal Growth Factor Receptor in ACC. Data of immune checkpoint blockade with nivolumab, ipilimumab, pembrolizumab and avelumab is explored in detail. Genomic studies indicate that up to 40% of ACC are driven by dysregulated WNT and glucocorticoid signaling, special focus is placed on emerging drugs in these pathways.

Expert opinion: Progress in the treatment of ACC has faced challenges stemming from the rarity of the disease. Given recent advances in the understanding of the molecular pathogenesis of ACC, a window of opportunity has now opened to make significant progress in developing therapeutic options that target key pathways such as excessive glucocorticoid signaling, WNT signaling, cell cycle and immune checkpoints.

KEYWORDS:

• Adrenocortical cancer
• immune checkpoint inhibitor
• targeted therapy
• WNT
• relacorilant

Declaration of interest

Manisha H. Shah declares research funding from Merck and Eli-Lilly. B Konda has received research funding to their institution from Bristol-Myers Squibb, Eli Lilly & Co., Merck, Eisai, and Xencor. L Kirschner is an advisory board member for Corcept Therapeutics. The author(s) have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded