Metabolic plasticity in the pancreatic cancer metastatic cascade

Most deaths from pancreatic ductal adenocarcinoma (PDAC) result from metastatic organ failure rather than primary tumor burden. Across the metastatic cascade, tumor cells encounter hypoxia, nutrient limitation, oxidative stress, immune pressure, and changing stromal conditions, and only those capable of dynamic metabolic adaptation successfully disseminate and colonize distant sites. In this review, we summarize how metabolic plasticity shapes PDAC dissemination, organ-specific colonization, and metastatic outgrowth. We further discuss how this framework may shift therapeutic strategy from broad metabolic blockade toward precision interventions that target metastatic fitness.