Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism

• DOI: 10.1038/ncomms15965
• Publication Date: 2017-07-03T09:42:32Z
• Authors: Douglas E. Biancur; Joao A. Paulo; Beata Małachowska; Maria Quiles Del Rey; Cristovão M. Sousa; Xiaoxu Wang; Albert S. W. Sohn; Gerald C. Chu; Steven P. Gygi; J. Wade Harper; Wojciech Fendler; Joseph D. Mancias; Alec C. Kimmelman
• Keywords: Glutaminase; Glutaminolysis; Metabolic pathway

Pancreatic ductal adenocarcinoma is a notoriously difficult-to-treat cancer and patients are in need of novel therapies. We have shown previously that these tumours altered metabolic requirements, making them highly reliant on number adaptations including non-canonical glutamine (Gln) pathway inhibition downstream components Gln metabolism leads to decrease tumour growth. Here we test whether recently developed inhibitors glutaminase (GLS), which mediates an early step metabolism, represent viable therapeutic strategy. show despite marked effects vitro proliferation caused by GLS inhibition, pancreatic cells adaptive networks sustain vivo. use integrated metabolomic proteomic platform understand this response thereby design rational combinatorial approaches. demonstrate targeting combination with responses may yield clinical benefits for patients.