Division of Endocrinology, Diabetes, and Metabolism, Arthur G. James Comprehensive Center, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Endocrine. 2020 Oct;70(1):24-35. doi: 10.1007/s12020-020-02453-8. Epub 2020 Aug 11.
Distant metastasis classically has been defined as a late-stage event in cancer progression. However, it has become clear that metastases also may occur early in the "lifetime" of a cancer and that they may remain stable at distant sites. This stability of metastatic cancer deposits has been termed "metastatic dormancy" or, as we term it, "metastatic progression dormancy" as the progression either may reflect growth of already existing metastases or new cancer spread. Biologically, dormancy is the presence of nongrowing, static metastatic cells that survive over time. Clinically, dormancy is defined by stability in tumor markers, imaging, and clinical course. Metastatic well-differentiated thyroid cancer offers an excellent tumor type to understand these processes for several reasons: (1) primary therapy often includes removal of the entire gland with ablation of residual normal tissue thereby removing one source for new metastases; (2) the presence of a sensitive biochemical and radiographic monitoring tests enabling monitoring of metastasis throughout the progression process; and (3) its tendency toward prolonged clinical dormancy that can last for years or decades be followed by progression. This latter factor provides opportunities to define therapeutic targets and/or markers of progression. In this review, we will discuss concepts of metastatic progression dormancy and the factors that drive both long-term stability and loss of dormancy with a focus on thyroid cancer.
远处转移通常被定义为癌症进展的晚期事件。然而，现在已经很清楚，转移也可能在癌症的“生命周期”早期发生，并且它们可能在远处保持稳定。这种转移性癌症沉积物的稳定性被称为“转移性休眠”，或者正如我们所说的，“转移性进展休眠”，因为进展可能反映已经存在的转移或新的癌症扩散。从生物学上讲，休眠是指非生长的、静止的转移性细胞随着时间的推移而存活。从临床上看，休眠是通过肿瘤标志物、影像学和临床过程的稳定性来定义的。分化良好的甲状腺癌转移提供了一个极好的肿瘤类型来理解这些过程，原因有几个：(1) 原发性治疗通常包括切除整个腺体并消融残留的正常组织，从而消除新转移的一个来源；(2) 存在敏感的生化和放射性监测测试，使转移在整个进展过程中得到监测；(3) 它倾向于长期临床休眠，可持续数年或数十年，随后进展。后一个因素为确定治疗靶点和/或进展标志物提供了机会。在这篇综述中，我们将讨论转移性进展休眠的概念，以及驱动长期稳定性和休眠丧失的因素，重点是甲状腺癌。
