文章：

肿瘤中的衰老：来自小鼠和人类的证据

Senescence in tumours: evidence from mice and humans

原文发布日期：2010-01-01

DOI: 10.1038/nrc2772

类型: Review Article

开放获取: 否

要点：

1. Senescence is a stress response prevalent in the aberrant environment of tumours.
2. Senescent cells are incapable of further proliferation and therefore tumour cell senescence is a brake to tumour progression.
3. A large body of evidence in mouse models indicates that in pre-malignant tumours most cells are senescent, therefore explaining the slow growth and low malignancy of these tumours. There are also examples of senescence in human pre-malignant tumours.
4. A class of tumour suppressors (for example, p53, INK4A and ARF) monitors stress signals, and the activation of these proteins triggers senescence. Their loss or inactivation is associated with impaired senescence, unleashing malignant progression.
5. Malignant tumours, despite their impaired ability to undergo senescence, can still be forced into senescence if crucial oncogenic pathways are disabled or tumour suppressors are restored.
6. Senescent tumour cells are rapidly cleared by immune cells, resulting in efficient tumour regression.
7. Senescence constitutes a new end point that might be relevant for the development of new drugs or prognostic markers and the evaluation of therapeutic treatments.

要点翻译：

1. 衰老是一种在肿瘤异常环境中普遍存在的应激反应。
2.  
3. 衰老细胞无法进一步增殖，因此肿瘤细胞衰老是抑制肿瘤进展的一种机制。大量小鼠模型证据表明，在恶性前期肿瘤中，大多数细胞处于衰老状态，这解释了这些肿瘤生长缓慢和恶性程度低的原因。在人类恶性前期肿瘤中也存在衰老的例证。
4. 一类肿瘤抑制因子（如p53、INK4A和ARF）监测应激信号，这些蛋白的激活会触发衰老。它们的缺失或失活与衰老功能受损相关，从而加速恶性进展。
5. 尽管恶性肿瘤的衰老能力受损，但如果关键致癌通路被阻断或肿瘤抑制功能得以恢复，仍可迫使肿瘤细胞进入衰老状态。
6. 衰老的肿瘤细胞会被免疫细胞迅速清除，从而实现有效的肿瘤消退。
7. 衰老作为一个新的终点，可能对开发新药物或预后标志物以及评估治疗效果具有重要意义。

英文摘要：

The importance of cellular senescence, which is a stress response that stably blocks proliferation, is increasingly being recognized. Senescence is prevalent in pre-malignant tumours, and progression to malignancy requires evading senescence. Malignant tumours, however, may still undergo senescence owing to interventions that restore tumour suppressor function or inactivate oncogenes. Senescent tumour cells can be cleared by immune cells, which may result in efficient tumour regression. Standard chemotherapy also has the potential to induce senescence, which may partly underlie its therapeutic activity. Although these concepts are well supported in mouse models, translating them to clinical oncology remains a challenge.

摘要翻译： 

细胞衰老的重要性正日益受到重视，这是一种稳定阻断增殖的应激反应。在癌前病变中普遍存在衰老现象，而进展为恶性肿瘤则需要逃避衰老。然而，由于恢复抑癌功能或失活癌基因的干预措施，恶性肿瘤仍可能发生衰老。衰老的肿瘤细胞可被免疫细胞清除，从而可能导致肿瘤高效消退。标准化疗也具有诱导衰老的潜力，这可能部分解释其治疗活性。尽管这些概念在小鼠模型中得到充分支持，但将其转化至临床肿瘤学仍面临挑战。

原文链接：

Senescence in tumours: evidence from mice and humans