Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine Anschutz Medical Campus Aurora.
Research Service, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA.
Curr Opin Endocrinol Diabetes Obes. 2020 Jun;27(3):170-176. doi: 10.1097/MED.0000000000000543.
The aim of this review is to summarize recent advances on development of in vivo preclinical models of adrenocortical carcinoma (ACC).
Significant progress has been achieved in the underlying molecular mechanisms of adrenocortical tumorigenesis over the last decade, and recent comprehensive profiling analysis of ACC tumors identified several genetic and molecular drivers of this disease. Therapeutic breakthroughs, however, have been limited because of the lack of preclinical models recapitulating the molecular features and heterogeneity of the tumors. Recent publications on genetically engineered mouse models and development of patient-derived ACC xenografts in both nude mice and humanized mice now provide researchers with novel tools to explore therapeutic targets in the context of heterogeneity and tumor microenvironment in human ACC.
We review current in-vivo models of ACC and discuss potential therapeutic opportunities that have emerged from these studies.
本综述旨在总结肾上腺皮质癌(ACC)体内临床前模型发展的最新进展。
在过去十年中,肾上腺皮质肿瘤发生的潜在分子机制取得了重大进展,最近对 ACC 肿瘤的综合分析确定了该疾病的几个遗传和分子驱动因素。然而,由于缺乏能够重现肿瘤分子特征和异质性的临床前模型,治疗上的突破受到限制。最近关于基因工程小鼠模型的出版物以及裸鼠和人源化小鼠中患者来源的 ACC 异种移植的发展,为研究人员提供了新的工具,可在人类 ACC 的异质性和肿瘤微环境背景下探索治疗靶点。
我们回顾了当前的 ACC 体内模型,并讨论了这些研究中出现的潜在治疗机会。