Kabak Evrim Ceren, Foo Sok Lin, Rafaeva Maria, Martin Ivan, Bentires-Alj Mohamed
Laboratory of Tumor Heterogeneity, Metastasis and Resistance, Department of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Adv Exp Med Biol. 2025;1464:373-395. doi: 10.1007/978-3-031-70875-6_18.
Breast cancer remission after treatment is sometimes long-lasting, but in about 30% of cases, there is a relapse after a so-called dormant state. Cellular cancer dormancy, the propensity of disseminated tumor cells (DTCs) to remain in a nonproliferative state for an extended period, presents an opportunity for therapeutic intervention that may prevent reawakening and the lethal consequences of metastatic outgrowth. Therefore, identification of dormant DTCs and detailed characterization of cancer cell-intrinsic and niche-specific [i.e., tumor microenvironment (TME) mediated] mechanisms influencing dormancy in different metastatic organs are of great importance in breast cancer. Several microenvironmental drivers of DTC dormancy in metastatic organs, such as the lung, bone, liver, and brain, have been identified using in vivo models and/or in vitro three-dimensional culture systems. TME induction and persistence of dormancy in these organs are mainly mediated by signals from immune cells, stromal cells, and extracellular matrix components of the TME. Alterations of the TME have been shown to reawaken dormant DTCs. Efforts to capitalize on these findings often face translational challenges due to limited availability of representative patient samples and difficulty in designing dormancy-targeting clinical trials. In this chapter, we discuss current approaches to identify dormant DTCs and provide insights into cell-extrinsic (i.e., TME) mechanisms driving breast cancer cell dormancy in distant organs.
乳腺癌治疗后的缓解有时是持久的，但在约30%的病例中，在所谓的休眠状态后会出现复发。细胞癌休眠，即播散性肿瘤细胞（DTCs）长时间保持非增殖状态的倾向，为治疗干预提供了机会，这种干预可能会防止DTCs重新激活以及转移灶生长带来的致命后果。因此，识别休眠的DTCs以及详细表征影响不同转移器官中休眠的癌细胞内在机制和微环境特异性机制（即肿瘤微环境介导的机制）在乳腺癌中至关重要。使用体内模型和/或体外三维培养系统已经确定了转移器官（如肺、骨、肝和脑）中DTC休眠的几种微环境驱动因素。这些器官中TME诱导和休眠的持续主要由TME中的免疫细胞、基质细胞和细胞外基质成分发出的信号介导。已表明TME的改变会使休眠的DTCs重新激活。由于代表性患者样本的可用性有限以及设计针对休眠的临床试验存在困难，利用这些发现的努力往往面临转化挑战。在本章中，我们讨论了识别休眠DTCs的当前方法，并深入探讨了驱动远处器官中乳腺癌细胞休眠的细胞外（即TME）机制。
