文章：

前列腺癌：炎性风暴

Prostate carcinogenesis: inflammatory storms

原文发布日期：2020-06-16

DOI: 10.1038/s41568-020-0267-9

类型: Review Article

开放获取: 否

英文摘要：

Haematopoiesis is governed by haematopoietic stem cells (HSCs) that produce all lineages of blood and immune cells. The maintenance of blood homeostasis requires a dynamic response of HSCs to stress, and dysregulation of these adaptive–response mechanisms underlies the development of myeloid leukaemia. Leukaemogenesis often occurs in a stepwise manner, with genetic and epigenetic changes accumulating in pre-leukaemic HSCs prior to the emergence of leukaemic stem cells (LSCs) and the development of acute myeloid leukaemia. Clinical data have revealed the existence of age-related clonal haematopoiesis, or the asymptomatic clonal expansion of mutated blood cells in the elderly, and this phenomenon is connected to susceptibility to leukaemic transformation. Here we describe how selection for specific mutations that increase HSC competitive fitness, in conjunction with additional endogenous and environmental changes, drives leukaemic transformation. We review the ways in which LSCs take advantage of normal HSC properties to promote survival and expansion, thus underlying disease recurrence and resistance to conventional therapies, and we detail our current understanding of leukaemic ‘stemness’ regulation. Overall, we link the cellular and molecular mechanisms regulating HSC behaviour with the functional dysregulation of these mechanisms in myeloid leukaemia and discuss opportunities for targeting LSC-specific mechanisms for the prevention or cure of malignant diseases.

摘要翻译： 

前列腺癌是癌症发病和死亡的主要原因。前列腺内炎症是前列腺癌发生的风险因素，与饮食、化学损伤及微生物组改变存在因果关联。前列腺内炎症细胞的募集与扩张最终可促进前列腺上皮细胞中的DNA双链断裂和雄激素受体激活。衰老相关分泌表型的激活会引发进一步的“炎症风暴”，自由基导致更多DNA损伤。这驱动DNA修复和肿瘤抑制基因的过度表达，使这些基因易受诱变损伤，而种系DNA修复基因缺陷会加速癌变过程。本文更新了前列腺癌发生机制的最新研究进展，并探讨基于这些发现的新型治疗和预防策略。

原文链接：

Prostate carcinogenesis: inflammatory storms