Stress granules-membraneless organelles as therapeutic targets in pancreatic cancer.

Therapies targeting pancreatic ductal adenocarcinoma (PDAC), driven in most cases by the KRAS oncogene, continue to present a clinical challenge. This emphasizes the need to explore alternative treatment paradigms in translational research. In this issue of EMBO Mol. Med., Santofimia-Castano et al, highlight that stress-inducible nuclear protein 1 (NUPR1), an intrinsically disordered protein, serves as a regulator of KRAS-associated stress granules (SGs) (Santofimia-Castaño et al, 2024). Targeting NUPR1 by a small molecule inhibitor prevents SG formation as well as the development and progression of pancreatic intraepithelial neoplasia (PanINs). Moreover, the NUPR1 inhibitor ZW-115 triggers apoptosis of PDAC cells dependent on KRAS expression. In essence, these findings are supportive of targeting SGs as a therapeutic approach for PDAC (Santofimia-Castaño et al, 2024).