ETD

• cancer stem cells
• glioblastoma
• motor cortex
• mouse model
• neuroscience
• preclinica phase
• therapy
• toxins

Glioblastoma Multiforme (GBM) is the most aggressive and malignant form of brain tumors. The therapeutic strategies currently used to counteract GBM are not effective and the consequent average survival is of about 15 months after diagnosis (Leece et al. 2017, Ostrom et al. 2019). Hence, there is an urgent need to identify innovative and effective therapeutic approaches that might produce a real impact on GBM patients’ survival and quality of life.
In Dr. Vannini’s lab has been recently designed and tested a chimeric protein, CTX-CNF1, as a potential drug to counteract GBM (Vannini et al. 2021). In vitro studies have highlighted that CTX-CNF1 induces senescence and death in both murine and human GBM cells, whereas in vivo studies had shown that CTX-CNF1 selectively targets glioma cells and increases glioma-bearing mice survival (Vannini et al. 2021). These experiments were performed on the classic and widely-used GL261 mouse model. However, experiments on different GBM models are required in order to understand whether the proposed therapeutic approach might represent an effective and solid strategy. Thus, in my Master Thesis I studied the effect of CTX-CNF1 treatment on another syngeneic mouse model of GBM. In this case, GBM was induced by injecting 50,000 CT2A cells (Casanova-Carvajal et al. 2019; 25,000/μl PBS) in the primary motor cortex (coordinates with respect to bregma: 500 µm anterior, 1750 µm lateral, 900 μm deep from pial surface) of C57BL6/J mice. In comparison with the GL261, the CT-2A is a more infiltrative and proliferative model. CT-2A cells also express stemness makers such as Nestin (Binello et al., 2012), indicating that this model is a valuable tool for pre-clinical testing of novel therapeutics. In both vehicle and CTX-CNF1 treated glioma-bearing animals, I longitudinally monitored motor performances using Grip Strength and Grid Walk tests, and tumoral mass growth through MRI. The ultimate goal of preclinical studies is to use animals to accurately model the biological effect of a drug, in order to predict a treatment outcome in patients and to identify and characterize all toxicities associated with the administration of the proposed drug (Polson and Fuji 2012). Thus, to this aim, testing drugs on different animal models is crucial before moving to clinics.