The adrenal glands are paired endocrine organs that produce steroid hormones and catecholamines required for life. 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's 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.

中文翻译：

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肾上腺皮质癌的生物学和基因组学更新：新兴疗法的基本原理。

肾上腺是成对的内分泌器官，产生生命所需的类固醇激素和儿茶酚胺。肾上腺皮质癌 (ACC) 是一种罕见且通常致命的癌症，发生于腺体周围区域（肾上腺皮质）。最近对肾上腺发育、体内平衡和疾病的研究加深了我们对控制皮质生长和更新的细胞和分子程序的理解，揭示了在恶性肿瘤的早期和晚期阶段生理程序如何被劫持的重要线索。除了这些研究之外，检查肾上腺皮质肿瘤的全基因组方法也改变了我们对 ACC 生物学的理解，并揭示 ACC 由与良好、中等和不良临床结果相关的不同分子亚型组成。每种 ACC 亚型中普遍存在的同质转录和表观遗传程序表明，它们可能对大量现有和新型靶向药物中的任何一种都敏感，但需要注意的是，治疗反应最终可能会受到癌细胞可塑性的限制。尽管过去十年生物医学研究取得了巨大进展，但迄今为止 ACC 唯一可能治愈的疗法是初次手术切除，高达 75% 的患者将出现标准护理辅助米托坦和细胞毒性化疗难治的转移性疾病。对我们领域对肾上腺皮质生理学和肿瘤的研究进行全面、综合和最新的临床了解对于开发新的临床工具和方法来帮助百万分之一的患者对抗这种毁灭性的疾病至关重要。