The management of adrenocortical carcinoma in the era of precision medicine

Adrenocortical carcinoma (ACC) is a rare but highly aggressive malignancy of the adrenal cortex, with heterogeneous clinical behaviour and limited therapeutic efficacy in advanced disease. While surgical resection remains the mainstay of curative treatment for localized tumours, outcomes in metastatic ACC remain poor, with long-term disease control achieved only in a minority of patients. Recent multi-omic studies have uncovered distinct molecular subtypes of ACC, providing deeper insight into tumor biology and potential therapeutic vulnerabilities. However, the translation of these molecular findings into clinical decision-making remains limited. This review offers a comprehensive and clinically relevant synthesis of current knowledge on ACC, with a specific focus on how molecular profiling can refine diagnosis, prognosis, and treatment strategies. We discuss current gaps, implementation challenges, and future directions toward a precision oncology approach for ACC.