THERAPEUTIC ADVANCES AND MULTIMODAL APPROACH IN THE TREATMENT OF GLIOBLASTOMA MULTIFORME

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and common primary central nervous system tumor in adults, characterized by a poor prognosis and a median survival that rarely exceeds 23 months. Its biology is marked by molecular heterogeneity, high invasive capacity, and therapeutic resistance, driven by the blood-brain barrier (BBB). Although the standard Stupp protocol (based on surgery, radiotherapy, and temozolomide) remains the gold standard treatment, this narrative literature review, based on recent evidence from PubMed, synthesizes advances towards a multimodal approach. Innovations include molecular stratification, particularly the isocitrate dehydrogenase (IDH) enzyme status, which has become a cornerstone for therapeutic decision-making; the development of immunotherapies such as CAR-T/CAR-NK cells and personalized RNA vaccines; and strategies to cross the BBB, such as focused ultrasound (MRgFUS) and nanomedicine. Furthermore, the identification of targets such as adrenomedullin (ADM) signaling in hypoxic macrophages points to vascular normalization as a relevant adjuvant strategy. The future of GBM management lies in the synergistic integration of mechanical eradication, immune modulation, and intelligent drug delivery systems, aiming for a transition to precision medicine capable of making the disease chronic.