biostudies-literatureUnknown8Gaglio DMinistero dell’Istruzione, dell’Università e della Ricerca<h4>Abstract</h4><h4>Background</h4>Rewiring of metabolism induced by oncogenic <i>K-Ras</i> in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways.<h4>Methods</h4>We performed mass spectrometric metabolomics analysis in vitro and in vivo experiments to evaluate the efficacy of drugs and identify metabolic connectivity.<h4>Results</h4>We show that <i>K-Ras</i>-mutant lung and colon cancer cells exhibit a distinct metabolic rewiring, the latter being more dependent on respiration. Combined treatment with the glutaminase inhibitor CB-839 and the PI3K/aldolase inhibitor NVCancer & metabolism22https://www.ebi.ac.uk/biostudies/studies/S-EPMC7523077biostudies-literatureDisruption of redox homeostasis for combinatorial drug efficacy in <i>K-Ras</i> tumors as revealed by metabolic connectivity profiling.PMC7523077Napodano EValtorta SPapa FCamboni TMetallo CMColangelo AMAlberghina LPaci PRaccagni IMoresco RMVanoni MBharat RParker SJConte FBonanomi MRighi NCifola IFiscon GRipamonti MGaglio DfalseDisruption of redox homeostasis for combinatorial drug efficacy in <i>K-Ras</i> tumors as revealed by metabolic connectivity profiling.<h4>Abstract</h4><h4>Background</h4>Rewiring of metabolism induced by oncogenic <i>K-Ras</i> in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways.<h4>Methods</h4>We performed mass spectrometric metabolomics analysis in vitro and in vivo experiments to evaluate the efficacy of drugs and identify metabolic connectivity.<h4>Results</h4>We show that <i>K-Ras</i>-mutant lung and colon cancer cells exhibit a distinct metabolic rewiring, the latter being more dependent on respiration. Combined treatment with the glutaminase inhibitor CB-839 and the PI3K/aldolase inhibitor NV2020-01-01T00:00:00Z20202025-05-29T22:10:12.629Z2025-05-29T22:10:12.629ZS-EPMC75230773300540110.1186/s40170-020-00227-4