文章：

胰腺癌中上皮和基质的共同进化及其共犯

Epithelial and stromal co-evolution and complicity in pancreatic cancer

原文发布日期：2022-11-29

DOI: 10.1038/s41568-022-00530-w

类型: Review Article

开放获取: 否

英文摘要：

Pancreatic ductal adenocarcinomas are distinguished by their robust desmoplasia, or fibroinflammatory response. Dominated by non-malignant cells, the mutated epithelium must therefore combat, cooperate with or co-opt the surrounding cells and signalling processes in its microenvironment. It is proposed that an invasive pancreatic ductal adenocarcinoma represents the coordinated evolution of malignant and non-malignant cells and mechanisms that subvert and repurpose normal tissue composition, architecture and physiology to foster tumorigenesis. The complex kinetics and stepwise development of pancreatic cancer suggests that it is governed by a discrete set of organizing rules and principles, and repeated attempts to target specific components within the microenvironment reveal self-regulating mechanisms of resistance. The histopathological and genetic progression models of the transforming ductal epithelium must therefore be considered together with a programme of stromal progression to create a comprehensive picture of pancreatic cancer evolution. Understanding the underlying organizational logic of the tumour to anticipate and pre-empt the almost inevitable compensatory mechanisms will be essential to eradicate the disease.

摘要翻译： 

胰腺导管腺癌以其显著的促纤维增生性反应（或称纤维炎症反应）为特征。该微环境主要由非恶性细胞主导，因此突变的上皮细胞必须对抗、协同或利用周围细胞及信号传导过程。有观点认为，侵袭性胰腺导管腺癌体现了恶性与非恶性细胞及机制的协同演化——这些机制通过破坏和重构正常组织的组成结构、空间构象和生理功能来促进肿瘤发生。胰腺癌复杂的动力学特征和渐进式发展规律提示其受到一套独特的组织规则和原理支配，而针对微环境中特定成分的反复靶向尝试揭示了其自我调节的耐药机制。因此，在构建胰腺癌演化全景图时，必须将转化导管上皮的组织病理学与遗传学进展模型同间质进展程序相结合。唯有理解肿瘤深层的组织逻辑，预判并阻断其几乎必然发生的代偿机制，才能实现对该疾病的根除。

原文链接：

Epithelial and stromal co-evolution and complicity in pancreatic cancer