Defining and Targeting Adaptations to Oncogenic KRASG12C Inhibition Using Quantitative Temporal Proteomics
Naiara Santana-Codina, Amrita Singh Chandhoke, Qijia Yu, Beata Małachowska, Miljan Kuljanin, Ajami Gikandi, Marcin Stańczak, Sebastian Gableske, Mark P. Jedrychowski, David A. Scott, Andrew J. Aguirre, Wojciech Fendler, Nathanael S. Gray, Joseph D. Mancias
Abstract
-driven tumors. Based on these proteomic data, we identify potent combinations of KRASi with phosphatidylinositol 3-kinase (PI3K), HSP90, CDK4/6, and SHP2 inhibitors, in some instances converting a cytostatic response to KRASi monotherapy to a cytotoxic response to combination treatment. Overall, using quantitative temporal proteomics, we comprehensively characterize adaptations to KRASi and identify combinatorial regimens with potential therapeutic utility.
Topics & Concepts
ProteomicsKRASProteomeComputational biologyQuantitative proteomicsBiologyPancreatic cancerBioinformaticsCancer researchCancerColorectal cancerBiochemistryGeneGeneticsAdvanced Proteomics Techniques and ApplicationsPeptidase Inhibition and AnalysisProtein Kinase Regulation and GTPase Signaling