Abstract A42: Exploring Differential Metabolic Plasticity for Treatment of Cancer

Abstract The metabolic properties of cancer cells diverge significantly from those of normal cells. Energy production in cancer cells is abnormally dependent on aerobic glycolysis even in the presence of sufficient oxygen concentration to perform OXPHOS in mitochondria. In the last years the understanding of cancer metabolism has increased, revealing its high complexity. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Emerging evidence shows that many features characteristic to cancer cells, such as deregulated Warburg-like glucose metabolism, fatty acid synthesis and glutaminolysis are linked to therapeutic resistance in cancer treatment. Therefore recently, there is a renewed interest in targeting metabolism as a resource for cancer treatment options. However, cancer heterogeneity and the variable mutational spectrum of cancer will likely hamper targeting metabolism in a manner similar to targeting deregulated signal transduction. Our work aims to analyze and correlate common cancer mutations with metabolic changes and thereby to rationalize metabolic personalized cancer treatment. For this purpose we combine metabolic measurements from genetically defined colon organoids (tumor progression organoid model and organoids derived from various genetically modified mice) and patient derived colon tumor organoids (biobank) from which the genome has been fully sequenced. Metabolism is profiled by various methods including Seahorse technology for the determination of bioenergetics, and untargeted metabolomics. This enables us to profile these organoids based on their metabolic program and to use this information for specific cancer treatment. Citation Format: Maria J. Rodriguez-Colman, Maaike Meerlo, Nanda Verhoeven-Duif, Boudewijn Burgering. Exploring differential metabolic plasticity for treatment of cancer. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A42.