Metastatic pancreatic cancer: from human disease to preclinical modelling.

Abstract

Metastatic pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid cancers, portending poor patient outcomes due to challenges in precise diagnosis and therapeutic resistance. Extensive molecular heterogeneity of metastatic tumours and their frequent evasion from clinical detection represent critical bottlenecks in disease management. Despite substantial research efforts, optimal clinical management remains an ongoing challenge. In this review, we outline the current understanding of metastatic pancreatic cancer, including its clinical features in patients. Emerging evidence highlights the pivotal roles of dynamic interactions between cancer cells and organ-specific and niche-specific microenvironments during metastatic spread. We further summarise the known molecular characteristics of metastatic PDAC and the preclinical models developed in pancreatic cancer research for functional interrogation. Finally, based on the current knowledge of this disease, we discuss existing limitations and future opportunities for advancing precision oncology approaches. These efforts may open promising avenues for the development of more effective clinical strategies aimed at mitigating metastasis in PDAC.