Manipulating the redox status in cancer cells to increase or restore the sensitivity towards chemo- and radiotherapies
Project: The main objective of this project is to test the additive/synergistic effects of proteasome inhibitors or radiation in combination with molecules that modify the redox status of tumor cells by generating ROS (reactive oxygen species). Anti-cancer therapies capable of generating ROS directly or indirectly (proteasome inhibitors, radiations) display a good efficacy but it is accompanied by toxicity and often resistance. ROS are generated in the cell either by an increase in mitochondrial activity and/or the activation of NOX complexes (NADPH oxidases), on one hand, or by the inhibition of antioxidant system, on the other hand. We propose to modify the redox equilibrium of tumor cells by targeting the antioxidant system and to analyze how this imbalance could increase the pro-apoptotic effects obtained with the molecules used in clinic or radiations. In order to validate our hypothesis, we will first analyze the response of multiple myeloma (MM) and mantle cell lymphoma cells (MCL), tumor models that respond perfectly to the induction of ROS by proteasome inhibitors.
Our work could provide the basis for introducing new molecules as therapeutic options in combination with other therapies in the treatment of MM and MCL. But more generally, the question of whether to antagonize or, conversely, promote oxidative stress in a therapeutic strategy is not yet resolved. Targeting the redox metabolism in tumor cells could be a promising strategy.
The project will be carried out at UFR Santé (Université de Caen Normandie). It will benefit from ICORE technological platform (http://www.icore.unicaen.fr/) and the lab expertise in cell biology and animal models.
We are looking for students with a strong motivation to carry out experimental research and a solid background in cell biology. During the project the student will be under contract with the Ecole Doctorale Normande BISE (https://www.unicaen.fr/ednbise/Accueil/) and will benefit of specialized trainings.
Applicants should submit their complete application file with:
– a curriculum vitae,
– a cover letter detailing their motivation and skills to take over the project,
– an abstract of their master project,
– and license (L3) and master (M1 and M2) ranking and notes in one pdf file by mail. The application dead line is 06/06/2018.
Position taken: September 2018
Assignment: INSERM UMR1245, MICAH team, Université de Caen Normandie
Location: CHU Côte de Nacre, Caen
Founding : 3-year PhD fellowship, a competitive exam is scheduled June 28 and 29, 2018