MOLECULAR MECHANISMS OF BRAIN TUMORIGENESIS: UNDERSTANDING THE ROLE OF GENETIC MUTATIONS AND TUMOR MICROENVIRONMENT IN GLIOBLASTOMA AND OTHER BRAIN CANCERS

Abstract

Brain tumors account, chiefly, for glioblastoma or GBM which are aggressive tumors that offer limited treatment options. The causative factors occur in highly complicated biological mechanisms like genetic mutations and changes occurring in the tumor microenvironment (TME). The discussion here revolves around the most controversial genetic drivers, including TP53, EGFR, IDH1/2, and PTEN mutations, as well as epigenetic modifications contributing to tumor development. The input will also extend into TME, including immune cells, components of extracellular matrices, and metabolic factors, which define progressive tumor development and therapy resistance. Also, emerging therapeutic approaches that target these pathways have all been addressed, thus providing some insights into promising advances to precision medicine for brain cancer treatment. Grasping the molecular mechanisms underscoring brain tumorigenesis is critical for devising efficacious therapeutic interventions. In addition to genetic mutations, which include TP53, EGFR, IDH1/2, and PTEN, the interaction of these mutations with their respective tumor microenvironments is critical for glioblastoma progression. Indeed, recent developments in targeted therapies, immunotherapy, and precision medicine hold great potential to improve patient outcomes. Still, the translation of such research into practice will need to address challenges such as resistance to therapy and blood-brain barrier limitations.