Glioblastoma multiforme (GBM) is the most aggressive and common primary brain cancer in adults. Its standard-of-care therapy encompasses surgical resection, radiotherapy, and chemotherapy. Although this combination therapy somewhat extends patient survival, its efficacy remains limited, and the recurrence rate remains high. In recent years, novel therapeutic approaches for the treatment of GBM have emerged: (i) tumor-treating fields delivering nonionizing low-intensity alternating electric fields to disrupt mitosis; (ii) molecular targeted therapies that inhibit specific gene mutations or signaling pathways; (iii) immunotherapy that activates the patient's own immune system to fight this cancer; (iv) proton therapy, which, with its precise radiation dose distribution, minimizes damage to the normal brain parenchyma surrounding the GBM; (v) oncolytic virus therapy to selectively infect and lyse GBM cells; (vi) the use of nanoparticle carriers for targeted drug delivery to increase therapeutic efficacy and reduce side effects; (vii) phototherapy; and (viii) sonodynamic therapy. The purpose of this narrative is to review both standard-of-care and novel contemporary approaches to this devastating cancer. In the future, with further advancements in multiomics technologies, artificial intelligence, and novel biomaterials, GBM treatment should move toward more personalized, precise, and comprehensive approaches, offering patients more effective treatment options.
Keywords: GBM; immunotherapy; molecular targeting; nanoparticle carriers; oncolytic viruses; personalized medicine; phototherapy; sonodynamic therapy; standard‐of‐care; tumor‐treating fields.
© 2025 International Society for Neurochemistry.