Current Pharmacotherapeutic Strategies in Diffuse Gliomas: Focus on Glioblastoma, IDH-Wildtype, and Emerging Targeted Therapies for IDH-Mutant Tumors

Glioblastoma, isocitrate dehydrogenase (IDH1/2) wild-type (IDH-wildtype), is one of the most aggressive and malignant tumors of the central nervous system, characterized by rapid growth, pronounced cellular heterogeneity, and an exceptionally poor prognosis. The median survival time for patients with glioblastoma, IDH-wildtype, is approximately 15 months after diagnosis, and current multimodal treatment strategies remain largely ineffective. This review focuses on contemporary pharmacotherapeutic approaches used in the management of glioblastoma, IDH-wildtype, including temozolomide-based chemotherapy, corticosteroids for edema control, and antiangiogenic therapy in recurrent disease, with particular emphasis on their clinical efficacy and limitations. In addition, the review discusses emerging targeted therapeutic strategies developed for IDH-mutant diffuse gliomas, which represent a biologically distinct disease entity. Particular attention is given to ivosidenib, a selective inhibitor of mutant IDH1, currently evaluated for the treatment of astrocytoma, IDH-mutant, grade 4. Its epigenetic mechanism of action, involving inhibition of the oncometabolite 2-hydroxyglutarate (2-HG), is outlined, along with preliminary clinical evidence suggesting potential to delay disease progression. Finally, innovative drug-delivery technologies designed to overcome the blood–brain barrier are briefly discussed as complementary strategies that may enhance the efficacy of both conventional and targeted therapies. Overall, future advances in the treatment of diffuse gliomas will likely depend on the integration of molecularly targeted agents, predictive biomarkers, and advanced delivery platforms aimed at improving patient survival and quality of life.