Yamu Li, Sulin Wu, Yiqing Zhao, Trang Dinh, Dongxu Jiang, J Eva Selfridge, George Myers, Yuxiang Wang, Xuan Zhao, Suzanne L Tomchuck, George Dubyak, Richard T Lee, Bassam Estfan, Marc Shapiro, Suneel D Kamath, Amr Mohamed, Stanley C-C Huang, Alex Y Huang, Ronald A Conlon, Smitha S Krishnamurthi, Jennifer R Eads, Joseph E Willis, Alok A Khorana, David L Bajor, Zhenghe Wang
Neutrophil Extracellular Traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and causes tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibits the growth of PIK3CA mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs. Disruption of NETs by either DNase I treatment or depletion of neutrophils in CRCs attenuated the efficacy of the drug combination...
January 9, 2024: Journal of Clinical Investigation