Purpose of review: Adrenocortical carcinoma is an aggressive, lethal malignancy of the adrenal cortex. The rarity of the disease has stymied therapeutic development. Recent work toward understanding the molecular pathogenesis of the disease has identified several potential new diagnostic and therapeutic targets.
Recent findings: The molecular characterization of adrenocortical carcinoma has identified dysregulation of the Gap 2/mitosis transition and the insulin-like growth factor 1 receptor signaling cascade as two major pathways for therapeutic development. These studies have also highlighted an unappreciated heterogeneity of the disease at the gene level that nevertheless seems to converge onto common cellular pathways. Additionally, the characterization of Wnt signaling through β-catenin in adrenal development, the demonstration of the involvement of BMP signaling in adrenocortical carcinoma growth regulation, and the discovery that ERCC1 expression levels can predict therapeutic response to platinum are just a few of the recent advances that promise to shed light on adrenocortical carcinoma biology.
Summary: Short-term, therapeutic development should target the Gap 2/mitosis transition and the downstream signaling of the insulin-like growth factor 1 receptor receptor. Long-term, additional characterization of patient samples, particularly at the sequence level, is required to fully understand adrenocortical carcinoma biology and apply that knowledge to clinical practice.