文章：

衰老微环境如何影响肿瘤进展

How the ageing microenvironment influences tumour progression

原文发布日期：2019-12-13

DOI: 10.1038/s41568-019-0222-9

类型: Review Article

开放获取: 否

英文摘要：

Most cancers arise in individuals over the age of 60. As the world population is living longer and reaching older ages, cancer is becoming a substantial public health problem. It is estimated that, by 2050, more than 20% of the world’s population will be over the age of 60 — the economic, healthcare and financial burdens this may place on society are far from trivial. In this Review, we address the role of the ageing microenvironment in the promotion of tumour progression. Specifically, we discuss the cellular and molecular changes in non-cancerous cells during ageing, and how these may contribute towards a tumour permissive microenvironment; these changes encompass biophysical alterations in the extracellular matrix, changes in secreted factors and changes in the immune system. We also discuss the contribution of these changes to responses to cancer therapy as ageing predicts outcomes of therapy, including survival. Yet, in preclinical studies, the contribution of the aged microenvironment to therapy response is largely ignored, with most studies designed in 8-week-old mice rather than older mice that reflect an age appropriate to the disease being modelled. This may explain, in part, the failure of many successful preclinical therapies upon their translation to the clinic. Overall, the intention of this Review is to provide an overview of the interplay that occurs between ageing cell types in the microenvironment and cancer cells and how this is likely to impact tumour metastasis and therapy response.

摘要翻译： 

大多数癌症发生于60岁以上人群。随着世界人口寿命延长及老龄化程度加剧，癌症正成为一个重大的公共卫生问题。据估计，到2050年，全球超过20%的人口将超过60岁——这可能给社会带来的经济、医疗保健和财政负担绝非小事。本篇综述中，我们将探讨衰老微环境在促进肿瘤进展中的作用。具体而言，我们将讨论衰老过程中非癌细胞发生的细胞和分子变化，以及这些变化如何促成肿瘤许可微环境；这些变化包括细胞外基质的生物物理改变、分泌因子的变化以及免疫系统的改变。我们还将讨论这些变化对癌症治疗反应的影响，因为衰老可预测治疗结局（包括生存期）。然而在临床前研究中，衰老微环境对治疗反应的影响大多被忽视——大多数研究设计采用8周龄小鼠，而非能反映疾病建模适宜年龄的老年小鼠。这可能部分解释了许多临床前研究成功的疗法在转化为临床治疗时失败的原因。总体而言，本综述旨在概述衰老微环境中各类细胞与癌细胞之间发生的相互作用，以及这种相互作用可能如何影响肿瘤转移和治疗反应。

原文链接：

How the ageing microenvironment influences tumour progression