The Group of Metabolism and Cell Signaling is interested in the mechanisms of interaction between cellular metabolism and processes of cell survival and growth to identify key elements involved in the adaptation of cancer cells to therapeutic treatments. We investigate the involvement of metabolic pathways in the control of cancer cell survival through their interaction with critical signaling pathways such as mTOR and Notch. We have already shown that a glutamine-mediated activation of mTORC1 signaling and inhibition of autophagy leads to cancer cell death and tumor regression during nutritional imbalance in both cellular and mouse models, due to a defective autophagic flux. (Villar et al., 2017 Nat Commun; Bodineau et al., 2021 Nat Commun).

We have also described an interaction between Notch signaling, glutamine metabolism and mTORC1 with potential therapeutic opportunities (Nguyen et al., Mol Oncol 2021; Bodineau et al., 2022 Autophagy; Zarzuela et al., 2023 Mol Oncol). In particular, glioblastoma, the most aggressive brain tumor with one of the highest mortality rates, still does not have an effective therapy. This lack of effectiveness is due to the high resistance to chemotherapy and rapid recurrence. Our current investigations aim at determining the metabolic, autophagic and cell signaling modifications that glioblastoma cells adopt to evade chemotherapy. Greater knowledge of the metabolic adaptability of glioblastoma cells can be exploited to sensitize them to treatment. To date, our studies in cellular, RNA-seq and metabolomic models, among others, show a differential response to glutamine imbalance and a genetic and metabolic reprogramming to the treatment that opens new therapeutic opportunities.