Linde N, Fluegen G, Aguirre-Ghiso J A
Tisch Cancer Institute, Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY, United States.
Adv Cancer Res. 2016;132:45-71. doi: 10.1016/bs.acr.2016.07.002. Epub 2016 Aug 25.
The majority of cancer deaths are due to metastases that can occur years or decades after primary tumor diagnosis and treatment. Disseminated tumor cells (DTCs) surviving in a dormant state in target organs appear to explain the timing of this phenomenon. Knowledge on this process is important as it might provide a window of opportunity to prevent recurrences by eradicating dormant DTCs and/or by maintaining DTCs in a dormant state. Importantly, this research might offer markers of dormancy for early monitoring of metastatic relapse. However, our understanding of the mechanisms underlying the regulation of entry into and exit from dormancy is still limited and crippling any therapeutic opportunity. While cancer cell-intrinsic signaling pathways have been linked to dormancy regulation, it is likely that these pathways and the switch controlling reactivation from dormancy are regulated by microenvironmental cues. Here we review and discuss recent findings on how the microenvironment regulates cancer dormancy and raise new questions that may help advance the field.
大多数癌症死亡是由转移导致的，转移可能发生在原发性肿瘤诊断和治疗后的数年或数十年。在靶器官中处于休眠状态存活的播散肿瘤细胞（DTC）似乎可以解释这一现象发生的时间。了解这一过程很重要，因为它可能提供一个机会窗口，通过根除休眠的DTC和/或使DTC维持在休眠状态来预防复发。重要的是，这项研究可能会提供休眠标志物，用于早期监测转移复发。然而，我们对进入和退出休眠调控机制的理解仍然有限，这削弱了任何治疗机会。虽然癌细胞内在信号通路与休眠调控有关，但这些通路以及控制从休眠中重新激活的开关很可能受微环境信号的调节。在此，我们回顾并讨论了关于微环境如何调节癌症休眠的最新发现，并提出了可能有助于推动该领域发展的新问题。
