GlioPATH: Comparison of central metabolic routes and signaling pathways in IDH mutant and wildtype gliomas (WHO °II-IV)

Malignant gliomas belong to the most feared types of cancer, due to their dismal prognosis, as well as direct consequences on cognitive function and quality of life. The mutation of isocitrate dehydrogenase (IDHmut) is of high prognostic relevance in malignant glioma. The IDH status has been connected with altered tryptophan (Trp) metabolism but the mechanism is unknown. Trp is intertwined with central cancer metabolism (nicotinamide adenine dinucleotide, NAD) and signaling pathways (mammalian target of rapamycin, mTOR; aryl hydrocarbon receptor, AHR), but their dynamic interplay and specific impact on drug responses remains elusive. A systems medicine approach integrating these central metabolic and signaling routes with clinical outcomes is currently missing. GlioPATH is an interdisciplinary (biomedical, theoretical, clinical) and synergistic team effort. Iterative computational-experimental approaches will establish the IDH-Trp-NAD-AHR- mTOR network structure and dynamics by integrating several existing data layers (transcriptomics, proteomics, epigenetic, clinical) from TCGA database with metabolomic and kinetic biochemical analyses of glioma tissues (NCT tissue bank). GlioPATH will enable an improved understanding of gliomagenesis and provide the basis to identify possible combinatorial intervention strategies for individualized glioma therapy. GlioPATH will allow us to establish an innovative scientific network by fostering horizontal knowledge transfer within our network and with the systems medicine community.