Pancreatic cancer is an exceptionally lethal cancer that is notoriously treatment resistant, in part due to poor vascularization in the tumor microenvironment. Investigators working at the Moores Cancer Center at the University of California, San Diego (UCSD), reported in the Jan. 16, 2023, issue of Nature Cell Biology on the discovery of a pathway that was initiated by isolation stresses (e.g., hypoxia, nutrient deprivation, and/or lack of extracellular matrix, ECM) leading to this cellular transformation in the tumor-initiating pancreatic cancer cell.