The group is devoted to two on-going projects:
i) research in glioblastoma (GBM), GBM is the highest-grade glioma, characterized by a rapid growth rate and an extensive infiltration into the surrounding brain tissue. In this context, in the last years the research group focused their interest in unveiling the mechanisms by which GBM tumor microenvironment (i.e. hypoxia) influences the activation of many developmental pathways and how their modulation impacts GBM biology. Based on our recent publication describing how the molecular crosstalk between HIF-1α and Wnt pathways is able to control GBM cell phenotype and aggressiveness (Boso et al., Theranostics 2019), our more recent studies in the field are devoted to explore the pharmacological inhibition of the β-catenin co-factor TCF4 as a reliable tool to induce glioblastoma cell differentiation and sensitization to chemotherapy. In particular, we identified the histone deacetylase inhibitors of the hydroxamate class Trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA) as potent inhibitors of TCF4 levels in glioblastoma cells. Based on this, they are being characterized for the effects on cell phenotype, the response to additional drug used for glioma therapy such as temozolomide and the molecular mechanisms potentially involved in these processes (supported by the Umberto Veronesi Foundation).
ii) research in medulloblastoma (MB). MB is the most common malignant brain tumor of childhood. Although survival has slowly increased in the past years, the prognosis of these patients remains unfavorable, with most of them suffering from high morbidity due to the high-dose chemotherapy/radiotherapy regimens they are subjected to. In the past years, our research on pediatric MB has been focused in the study of the intracellular signaling pathways, commonly activated during embryonic cerebellar development, which could have a role in sustaining MB cell biology including Notch signaling (Pistollato et al. Stem Cells 2010) and the PI3K/AKT/mTOR axis (Frasson et al. Biomed Res Int 2015). More recently, our group established novel in vitro models of MB drug resistance, which offer an invaluable opportunity for identifying actionable targets, which may have been masked in the original untreated cells. Based on this knowledge, a recent research line supported by the Rally Foundation for Childhood Cancer Research is devoted to exploit these drug-resistant MB models for a high-throughput screening of multiple FDA-approved compound libraries with the final aim of prioritizing clinically approved agents for the use in therapy-resistance MB cells and their future clinical development. In this context, the recent achievement of a pediatric research grant from CARIPARO Foundation will allow to get a deep molecular insight in the process of drug resistance acquisition of these tumors through the single-cell analysis of their transcriptional dynamics during the acquisition of a chemotherapy resistant phenotype. Moreover, through the use of reliable models of chemotherapy resistance, coupled to the most recent single-cell analysis technologies we will analyze the molecular events contributing to MB drug resistance and integrate transcriptomic data with epitope mapping to perform backtracking of cell population dynamics and provide multi-omics-based risk assessment and prognostication of treatment response potentially even at MB diagnosis.