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Adrenocortical carcinoma (ACC) is a rare and often fatal cancer of the peripheral domain of the gland, the adrenal cortex. Recent research in adrenal development, homeostasis, and disease have refined our understanding of the cellular and molecular programs controlling cortical growth and renewal, uncovering crucial clues into how physiologic programs are hijacked in early and late stages of malignant neoplasia. Alongside these studies, genome-wide approaches to examine adrenocortical tumors have transformed our understanding of ACC biology, and revealed that ACC is composed of distinct molecular subtypes associated with favorable, intermediate, and dismal clinical outcomes. The homogeneous transcriptional and epigenetic programs prevailing in each ACC subtype suggest likely susceptibility to any of a plethora of existing and novel targeted agents, with the caveat that therapeutic response may ultimately be limited by cancer cell plasticity. Despite enormous biomedical research advances in the last decade, the only potentially curative therapy for ACC to date is primary surgical resection, and up to 75% of patients will develop metastatic disease refractory to standard-of-care adjuvant mitotane and cytotoxic chemotherapy. A comprehensive, integrated, and current bench-to-bedside understanding of our field\u2019s investigations into adrenocortical physiology and neoplasia is crucial to developing novel clinical tools and approaches to equip the one-in-a-million patient fighting this devastating disease.<\/jats:p>","DOI":"10.1210\/endrev\/bnac012","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T10:05:57Z","timestamp":1652436357000},"page":"1051-1073","source":"Crossref","is-referenced-by-count":34,"title":["Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies"],"prefix":"10.1210","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-6432","authenticated-orcid":false,"given":"Antonio Marcondes","family":"Lerario","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan , Ann Arbor, Michigan 48109-2200 , 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