Altered tumor metabolism is a hallmark of cancer and contributes to the plasticity of cancer cells enabling adaption to microenvironmental changes. In addition, some cancers are characterized by mutations in metabolic enzymes, as is the case for specific subtypes of diffuse gliomas, i.e. astrocytomas and oligodendrogliomas. Heterozygous mutations in NADP(+)-dependent isocitrate dehydrogenases (IDH) are driver mutations for these tumors and are associated with hypermethylation of DNA and chromatin. We are specifically interested in the metabolic aberrations and adaptation mechanisms adopted by these tumors with the aim to identify novel metabolic vulnerabilities of IDH mutant gliomas.
Using imaging mass spectrometry and LC-MS analysis in glioma patient and PDOX samples, we have characterized the metabolic landscape of these tumors and have identified major abnormalities in phospholipid and oxidative stress pathways. Based on these findings we are trying to understand the impact of altered fatty acid synthesis and address how oxidative stress pathways are maintained in IDH mutant gliomas.
This project is supported by the Luxembourg National Research Fund (PRIDE15/10675146/CANBIO) and the Fondation du Pélican de Mie and Pierre Hippert-Faber.