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Publication : Epithelial and stromal co-evolution and complicity in pancreatic cancer.

First Author  Hingorani SR Year  2023
Journal  Nat Rev Cancer Volume  23
Issue  2 Pages  57-77
PubMed ID  36446904 Mgi Jnum  J:332905
Mgi Id  MGI:7431042 Doi  10.1038/s41568-022-00530-w
Citation  Hingorani SR (2023) Epithelial and stromal co-evolution and complicity in pancreatic cancer. Nat Rev Cancer 23(2):57-77
abstractText  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.
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