Metabolomica e Trascrittomica Dei Gliomi a Basso ed Alto Grado (GlioMeTra) L2093

Diffuse gliomas, both lower-grade gliomas (LGG, WHO grade 2) and higher-grade gliomas (HGG, including grades 3 and 4 and glioblastomas (GBM, WHO grade 4), are highly infiltrative brain tumors that arise from glial progenitor cells and include astrocytomas, oligodendrogliomas, and GBMs. In the latest WHO 2021 classification of brain tumors, they are divided into three diagnostic and prognostic subtypes: i) isocitrate dehydrogenase 1 and 2 (IDH1/2) mutated and 1p/19q co-deleted (i.e., oligodendrogliomas), ii) IDH1/2 mutated and 1p/19q non-co-deleted (i.e., astrocytomas), and iii) IDH1/2 wildtype astrocytomas, including GBMs.

In current clinical practice, only IDH-mutated lesions are considered true LGG. Furthermore, some LGG can progress to WHO grade 4 (grade 4 astrocytomas) within a few months, while others remain stable and indolent for years, with an overall survival ranging from 1 to 15 years.

Therefore, being able to efficiently predict the clinical trajectories of LGG subgroups and personalize the care and treatment of these patients represents a significant unmet clinical need that requires accurate and robust patient stratification.

Similarly, recent studies have demonstrated the presence of molecular subgroups of GBM (transcriptional and metabolic in particular) that present different alterations in important pathways that can potentially be targeted pharmacologically, increasing the still too limited arsenal in the therapeutic management of these patients who still maintain an invariably poor prognosis.

Additionally, studies on gliomas rely on cellular cultures and animal models. These techniques, however, are effective for GBMs but are still severely unsuitable for generating LGG models, which nowadays are still lacking, despite being necessary to enable proper development of new medications.