文章：

癌症休眠的模型、机制和临床证据

Models, mechanisms and clinical evidence for cancer dormancy

原文发布日期：2007-11-01

DOI: 10.1038/nrc2256

类型: Review Article

开放获取: 否

要点：

1. In the clinic, tumour dormancy is observed in local recurrences or metastases. It usually refers to the time after treatment that a patient is asymptomatic but still carries local remnant or disseminated tumour cells that do not grow into overt lesions.
2. Tumour dormancy ensues when cancer cell proliferation is counteracted by other mechanisms such as apoptosis because of impaired vascularization or immunosurveillance, and cellular dormancy ensues when the cancer cells enter a growth arrest.
3. Cancer dormancy is a relevant problem because the majority of solid tumours and haematological malignancies undergo a period of dormancy that is characterized by years to decades of minimal residual disease. Because metastases always arise from disseminated tumour cells it is of importance to understand the biology of dormant tumour cells.
4. Several mechanisms can explain cancer dormancy. These include the disruption of crosstalk between growth factor and adhesion signalling, which prevents tumour cells from interpreting their microenvironment, leading to cellular tumour dormancy through a G0–G1 arrest or 'differentiation'; the inability of a tumour cell population to recruit blood vessels despite active proliferation; and immunosurveillance, which can prevent residual tumour cell expansion.
5. The expression of genes that selectively suppress metastases might function by inducing dormancy. In addition, quiescent tumour 'stem' cells might be dormant tumour cells. Finally, dormant tumour cells seem to have active drug resistance mechanisms that might protect them from therapy.
6. The therapeutic opportunities that emerge from understanding dormancy include the possibility of inducing and/or maintaining the dormancy of tumour cells and inducing cell death in residual dormant cells by targeting their survival and drug-resistance mechanisms.
7. Studies of cancer dormancy might help determine whether a patient has dormant disease and what type of mechanism is active. These studies will be instrumental in identifying biomarkers of dormant cancer.

要点翻译：

1. 在临床上，肿瘤休眠可见于局部复发或转移病例。它通常指患者在治疗后无症状期，体内仍携带局部残留或已播散的肿瘤细胞，但这些细胞并未发展成明显病灶。
2. 当癌细胞增殖被其他机制（如因血管化受损或免疫监视导致的细胞凋亡）抵消时，就会发生肿瘤休眠；而当癌细胞进入生长停滞状态时，则会出现细胞休眠。
3. 癌症休眠是一个重要课题，因为大多数实体瘤和血液系统恶性肿瘤都会经历休眠期，其特征是持续数年甚至数十年的微小残留病灶。由于转移灶总是来源于播散的肿瘤细胞，因此理解休眠肿瘤细胞的生物学特性至关重要。
4. 多种机制可解释癌症休眠现象：包括生长因子与黏附信号传导的串扰被破坏，导致肿瘤细胞无法解读微环境信号，进而通过G0-G1期阻滞或“分化”进入细胞休眠状态；肿瘤细胞群虽持续增殖却无法招募血管；以及免疫监视阻止残留肿瘤细胞扩增。
5. 选择性抑制转移的基因表达可能通过诱导休眠发挥作用。此外，静止的肿瘤“干细胞”可能就是休眠肿瘤细胞。最后，休眠肿瘤细胞似乎具有活跃的耐药机制，这可能保护它们免受治疗影响。
6. 通过理解休眠现象产生的治疗机遇包括：诱导和/或维持肿瘤细胞休眠状态，以及通过靶向其存活和耐药机制来诱导残留休眠细胞死亡。
7. 对癌症休眠的研究有助于判断患者是否存在休眠疾病，以及何种机制在发挥作用。这些研究将为鉴定休眠癌症的生物标志物提供重要支撑。

英文摘要：

Patients with cancer can develop recurrent metastatic disease with latency periods that range from years even to decades. This pause can be explained by cancer dormancy, a stage in cancer progression in which residual disease is present but remains asymptomatic. Cancer dormancy is poorly understood, resulting in major shortcomings in our understanding of the full complexity of the disease. Here, I review experimental and clinical evidence that supports the existence of various mechanisms of cancer dormancy including angiogenic dormancy, cellular dormancy (G0–G1 arrest) and immunosurveillance. The advances in this field provide an emerging picture of how cancer dormancy can ensue and how it could be therapeutically targeted.

摘要翻译： 

癌症患者可能在数年甚至数十年后出现复发转移，这种“暂停”现象可用癌症休眠解释：残余病灶存在但无症状。癌症休眠机制不清，阻碍了对疾病复杂性的全面理解。本文综述实验与临床证据，支持血管生成休眠、细胞休眠（G0–G1阻滞）和免疫监视等多种机制。该领域进展正逐步揭示休眠如何发生，以及如何成为治疗靶点。

原文链接：

Models, mechanisms and clinical evidence for cancer dormancy