CANCELLED Metabolic Flux Analysis for Cancer Personalized Medicine

2020/03/31 Atrio 800


CANCELLED Metabolic Flux Analysis for Cancer Personalized Medicine

CANCELLED Dra. Marta Cascante

CANCELLED Metabolic Flux Analysis for Cancer Personalized Medicine 1Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona (UB) and Institute of Biomedicine of University of Barcelona (IBUB), Barcelona. 2Centro de Investigación Biomédica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), Madrid. Introduction Despite advances in therapy, progression to metastasis and acquisition of resistance to chemotherapy remain the greatest challenges in cancer. More specifically, new modalities of treatment are urgently needed for metastatic cancer and to cope with acquired drug resistance. Recent studies have highlighted metabolic reprogramming as a key player in the acquisition of metastatic potential and therapeutic resistance, which has led to propose metabolic adaptations as potential therapeutic targets. Technological and methodological innovation Here, we have applied a systems biology approach, including experimental data integration into genome-scale metabolic models, to unveil metabolic differences and potential vulnerabilities associated with metabolic heterogeneity of tumor cells subpopulations in metastatic prostate cancer and to cisplatin resistance. For this purpose we use a dual model clonal cell model, consisting of a CSC-subpopulation with an epithelial phenotype and a non-CSC-subpopulation with hallmarks of stable EMT. Results and impact We show that EMT and metastasis programes can display distinct metabolic traits. Briefly, the major differences were observed in differential use of glucose and glutamine to fuel TCA cycle, mitochondrial respiration, one-carbon metabolism, beta-oxidation and eicosanoids metabolism. By applying similar approaches, we have identified metabolic adaptive responses associated with platinum resistance as actionable targets in combined therapeutic strategies. We concluded that, the novel genome-scale multiomics approach here proposed, permit to unveil new mechanisms of cancer cell adaptation whose targeting counteracts the acquisition of pharmacological resistance. Collaborators: M. TARRADO-CASTELLARNAU1,2,C. BALCELLS1,3, J. TARRAGO1,2 I. MARIN DE MAS1,4+, E. AGUILAR1+ , P. DE ATAURI1,2 , E. ZODDA1, M. PONS5, J. J. CENTELLES1,2, B. PAPP5, F. Mas3, M. MUÑOZ-ORDOÑO1,2, V. SELIVANOV1,2, J. PERARNAU1+, F. MORRISH6, D. HOCKENBERY6 , M. YUNEVA7 , S. MARIN1,2 ,T. THOMSON2,5 1Deptm. of Biochem. and Mol. Biomedicine, Fac. Biology, UB, and Institute of Biomedicine of UB (IBUB), Barcelona. 2 CIBEREHD), Instituto de Salud Carlos III (ISCIII), Madrid. 3Deptm. of Material Sciences and Physical Chemistry and Research Institute of Theoretical and Computational Chemistry (IQTCUB), Barcelona. 4Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged. 5Barcelona Institute for Molecular Biology (IBMB-CSIC), Barcelona. 6Fred Hutchinson Cancer Research Center, Seattle. 7The Francis Crick Institute, London. +Former affiliations were the work has been done.

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