Where It Spreads Matters: Molecular Drivers of Pancreatic Cancer Metastasis

A new multi-omic study in Nature Cancer reveals why pancreatic ductal adenocarcinoma (PDAC) patients with lung metastases survive longer than those with liver metastases. Despite sharing the same tumor subtype, the lung metastasis cohort showed stronger T cell clonal responses and higher lymphocyte infiltration, indicative of active tumor immunity. In contrast, liver-metastatic tumors exhibited heightened replication stress tolerance and immunosuppressive features. The authors defined a “primary organotropism” (pORG) gene set enriched in liver-targeting tumors, linking specific gene expression patterns to metastatic site preference. These findings point to distinct evolutionary pressures and immune landscapes that govern metastasis destination and patient outcomes in PDAC.