Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.
ISREC-Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Genesis. 2024 Feb;62(1):e23552. doi: 10.1002/dvg.23552. Epub 2023 Sep 30.
More than two-thirds of cancer-related deaths are attributable to metastases. In some tumor types metastasis can occur up to 20 years after diagnosis and successful treatment of the primary tumor, a phenomenon termed late recurrence. Metastases arise from disseminated tumor cells (DTCs) that leave the primary tumor early on in tumor development, either as single cells or clusters, adapt to new environments, and reduce or shut down their proliferation entering a state of dormancy for prolonged periods of time. Dormancy has been difficult to track clinically and study experimentally. Recent advances in technology and disease modeling have provided new insights into the molecular mechanisms orchestrating dormancy and the switch to a proliferative state. A new role for epithelial-mesenchymal transition (EMT) in inducing plasticity and maintaining a dormant state in several cancer models has been revealed. In this review, we summarize the major findings linking EMT to dormancy control and highlight the importance of pre-clinical models and tumor/tissue context when designing studies. Understanding of the cellular and molecular mechanisms controlling dormant DTCs is pivotal in developing new therapeutic agents that prevent distant recurrence by maintaining a dormant state.
超过三分之二的癌症相关死亡可归因于转移。在某些肿瘤类型中，转移可能在原发性肿瘤成功治疗和诊断后长达 20 年发生，这种现象被称为晚期复发。转移是由播散的肿瘤细胞（DTCs）引起的，这些细胞在肿瘤发展的早期就离开原发性肿瘤，无论是作为单细胞还是细胞簇，适应新的环境，并减少或关闭其增殖，进入休眠状态，持续很长时间。休眠状态在临床上很难追踪，在实验中也很难研究。最近技术和疾病建模方面的进展为调控休眠和向增殖状态转变的分子机制提供了新的见解。上皮-间充质转化（EMT）在几个癌症模型中诱导可塑性和维持休眠状态的新作用已经被揭示。在这篇综述中，我们总结了将 EMT 与休眠控制联系起来的主要发现，并强调了在设计研究时使用临床前模型和肿瘤/组织背景的重要性。了解控制休眠 DTC 的细胞和分子机制对于开发新的治疗药物至关重要，这些药物通过维持休眠状态来防止远处复发。
