Department of Surgery and Pharmacology, University of Colorado Comprehensive Cancer Center, Building 500, 13001 East 17th Place, Aurora, CO 80045, USA.
Nat Rev Clin Oncol. 2013 Jan;10(1):41-51. doi: 10.1038/nrclinonc.2012.207. Epub 2012 Nov 27.
The reactivation of cancer cells following a seemingly successful treatment of the primary tumour with initial therapies (such as tumour excision or systemic therapy) is a well-known phenomenon. This metastatic rebirth is preceded by an interlude, termed dormancy, when cancer sleeps undetected for periods that can last years or even decades. Discoveries over the past 10 years have revealed the therapeutic potential of prolonging dormancy for maintaining a clinically asymptomatic state, or the permanent clearance of dormant residual disseminated cancer cells to affect a 'cure'. Here, we provide an overview of the mechanisms of dormancy and use genitourinary cancers as models to demonstrate how dormancy principles could be exploited clinically. Data from these models have yielded promising therapeutic strategies to address dormancy as well as diagnostics that could enable clinicians to monitor the dormant state of cancer in patients. This Review also aims to convey that dormancy, as a whole, likely results from coalescing contributions made by each of the three types of dormancy discussed (cellular, angiogenic and immunological). In our opinion, dormancy-directed therapies will prove most effective when the effect of these cumulative contributions are understood and targeted.
癌症细胞在经过初始治疗(如肿瘤切除或全身治疗)后,在原发性肿瘤看似成功治疗后重新激活是一种众所周知的现象。这种转移性重生之前有一个间歇期,称为休眠期,在此期间,癌症在数年甚至数十年的时间里未被发现而处于休眠状态。在过去的 10 年中,人们发现了延长休眠期以维持临床无症状状态的治疗潜力,或者永久性清除休眠性播散性癌细胞以实现“治愈”。在这里,我们概述了休眠的机制,并以泌尿生殖系统癌症为例,展示了如何在临床上利用休眠原理。这些模型的数据产生了有前途的治疗策略来解决休眠问题,以及能够使临床医生监测患者癌症休眠状态的诊断方法。本综述还旨在传达这样一种观点,即休眠作为一个整体,可能是由所讨论的三种休眠类型(细胞、血管生成和免疫)的综合贡献共同作用的结果。在我们看来,当理解和靶向这些累积贡献的影响时,休眠定向疗法将被证明是最有效的。