New strategies for applying targeted therapies to adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare, aggressive, and frequently deadly cancer. Up to 75% of all patients will eventually develop metastatic disease, and our current medical therapies for ACC provide limited - if any - survival benefit. These statistics highlight a crucial need for novel approaches. Recent studies performing comprehensive molecular profiling on ACC have illuminated that ACC is comprised of three clinically distinct molecular subtypes, bearing differential regulation of cell cycle, epigenetics, Wnt/β-catenin signaling, PKA signaling, steroidogenesis and immune cell biology. Furthermore, these studies have spurred the development of molecular subtype-based biomarkers, contextualized outcomes of recent clinical trials, and advanced our understanding of the underlying biology of adrenocortical homeostasis and cancer. In this review, we describe these findings and their implications for new strategies to apply targeted therapies to ACC.