胰腺导管癌以其强大的纤维增生或纤维炎症反应而著称。由非恶性细胞主导，因此突变的上皮细胞必须与周围细胞和信号过程作战、合作或利用其微环境。作为恶性和非恶性细胞以及机制协调演化的结果，侵袭性胰腺导管癌被提出了以挫败和改变正常组织构成、结构和生理为促进肿瘤发生的目的。胰腺癌的复杂动力学和分步发展表明，它受到一组离散的组织规则和原则的支配，并反复尝试针对微环境内特定组分的靶向，揭示了自我调节机制的抵抗。因此，必须将转化性导管上皮的组织病理学和遗传进展模型与基质进展方案考虑在一起，以创建胰腺癌演变的全面图景。了解肿瘤的潜在组织逻辑，预期并预先防范几乎不可避免的补偿机制将是消灭疾病的关键。 © 2022 Springer Nature Limited。

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.© 2022. Springer Nature Limited.