An update on the molecular biology of glioblastoma, with clinical implications and progress in its treatment
Immunotherapy and neoantigen/nucleic‑acid vaccines are emerging strategies under active clinical investigation for glioblastoma treatment.
Glioblastoma multiforme (GBM) is the most aggressive and common malignant primary brain tumor. Patients with GBM often have poor prognoses, with a median survival of ~15 months. Enhanced understanding of the molecular biology of central nervous system tumors has led to modifications in their classifications, the most recent of which classified these tumors into new categories and made some changes in their nomenclature and grading system. This review aims to give a panoramic view of the last 3 years’ findings in glioblastoma characterization, its heterogeneity, and current advances in its treatment. Several molecular parameters have been used to achieve an accurate and personalized characterization of glioblastoma in patients, including epigenetic, genetic, transcriptomic and metabolic features, as well as age‑ and sex‑related patterns and the involvement of several noncoding RNAs in glioblastoma progression. Glioblastoma metabolism is characterized by upregulation of the PI3K/Akt/mTOR signaling pathway, promotion of the glycolytic flux, maintenance of lipid storage, and other features. This metabolism also contributes to glioblastoma's resistance to conventional therapies. Tumor heterogeneity, a hallmark of GBM, has been shown to affect the genetic expression, modulation of metabolic pathways, and immune system evasion. Ongoing clinical trials are investigating immunotherapy, PI3K/Akt/mTOR axis inhibitors, angiogenesis blockers and other targeted approaches.
Understanding and targeting the immune environment of glioblastoma may provide new therapeutic options for a tumor with very limited survival outcomes.
Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.