肾上腺皮质癌生物学和基因组学的最新进展:新兴疗法的基本原理。

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Antonio Marcondes Lerario, Dipika R Mohan, Gary D Hammer
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引用次数: 5

摘要

肾上腺是成对的内分泌器官,产生生活所需的类固醇激素和儿茶酚胺。肾上腺皮质癌(ACC)是一种罕见且往往致命的癌症,发生在肾上腺皮质的外周区域。最近对肾上腺发育、稳态和疾病的研究完善了我们对控制皮质生长和更新的细胞和分子程序的理解,揭示了恶性肿瘤早期和晚期生理程序如何被劫持的关键线索。除了这些研究之外,检查肾上腺皮质肿瘤的全基因组方法改变了我们对ACC生物学的理解,并揭示了ACC由不同的分子亚型组成,这些亚型与有利、中等和令人沮丧的临床结果有关。在每个ACC亚型中普遍存在的同质转录和表观遗传程序表明,可能对过多的现有和新靶向药物中的任何一种都有易感性,但需要注意的是,治疗反应最终可能受到癌症细胞可塑性的限制。尽管在过去十年中生物医学研究取得了巨大进展,但迄今为止,ACC唯一潜在的治疗方法是初次手术切除,高达75%的患者将发展为对标准护理辅助米托坦和细胞毒性化疗难以治疗的转移性疾病。对我们领域对肾上腺皮质生理学和肿瘤的研究有一个全面、综合和最新的了解,对于开发新的临床工具和方法来装备百万分之一的患者对抗这种毁灭性疾病至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.

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.

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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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