Aug 2026· Brain Stimulation· Vol 19, pp.
103189
· 0 citations· 107 references
Medicine
TL;DR
Biophysical therapies are best conceived as adjunctive tools within multimodal glioblastoma management rather than stand-alone solutions, with a strong focus on predictive biomarker-driven, mechanistically informed trial designs.
Abstract
Despite intensive multimodal treatment, outcomes in glioblastoma remain poor, with median overall survival typically limited to 14-18 months and only 5-10% of patients surviving beyond five years. These limitations have fueled interest in biophysical, device-based strategies that apply electric, magnetic, acoustic, optical, or thermal energy to modulate tumor biology and the immune microenvironment, while also enhancing systemic therapies. This review summarizes current concepts and evidence for major biophysical modalities in glioblastoma, emphasizing mechanistic rationale, translational maturity, and implications for trial design. Besides radiotherapy, Tumor Treating Fields (TTFields) therapy is the only noninvasive biophysical modality currently integrated into routine clinical practice, supported by randomized phase III survival data in newly diagnosed disease. Other modalities are at earlier stages of translation, including oscillating magnetic field (OMF) concepts targeting metabolic and oxidative-stress vulnerabilities; ultrasound-based platforms for reversible and focused blood-brain barrier (BBB) modulation, sonodynamic approaches, and focal ablation; photodynamic therapy combining photosensitizers with spatially controlled light activation; and thermal strategies such as laser interstitial thermal therapy and magnetic nanoparticle-mediated hyperthermia. Across modalities, key unresolved issues include parameter standardization and dosimetry, patient selection, interactions with chemoradiation and corticosteroids, feasibility and adherence in real-world settings, and the scarcity of controlled trials with clinically meaningful endpoints. Overall, biophysical therapies are best conceived as adjunctive tools within multimodal glioblastoma management rather than stand-alone solutions. Their integration into clinical practice should proceed cautiously, accompanied by an iterative cycle of translation and reverse translation, with a strong focus on predictive biomarker-driven, mechanistically informed trial designs.
The therapeutic landscape of targeted therapies in glioblastomas is summarized, spanning major target classes including receptor tyrosine kinases, intracellular signalling proteins, cell-cycle dysregulation and synthetic-lethal vulnerabilities and emerging strategies targeting genome integrity and telomeres, epigenetic modulators, and tumour-neural circuitry are examined.
E. Aquilanti, M. Touat, P. French et al.· Nature Reviews Clinical Onco...· 0 citations
This review systematically summarizes recent advances in nanomedicine enabled GBM therapy from four interrelated perspectives: the optimization of nanomaterial properties, the development of goal-oriented targeting strategies, the rationalization of delivery routes, and the engineering of smart stimuli-responsive nano-systems.
Yu Guo, Keqiang Lu, Wenmiao Luo et al.· Wiley Interdisciplinary Revi...· 1 citation
Sonodynamic therapy (SDT) has become an effective non-invasive treatment modality. This technique involves the selective activation of sonosensitizers by ultrasound (US) energy, leading to localized production of reactive oxygen species (ROS) and subsequent tumor cell death. Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive primary malignant tumors of the brain, posing a tremendous therapeutic challenge. Although the present treatment is a combination of maximum surgical resection, radiotherapy, and chemotherapy, prognosis is still poor with high recurrence rates. SDT has unique benefits for GBM therapy, specifically the capacity of low-intensity focused US to temporarily and reversibly breach the blood-brain barrier (BBB) to boost the targeted delivery of sonosensitizers and other medication. In addition, US offers high spatial specificity, allowing it to be localized to the tumor and causes minimal destruction to healthy tissue. Nonetheless, SDT has several limitations for clinical translation. These include suboptimal biodistribution and poor tumor-specific targeting of traditional sonosensitizers, attenuation, and distortion of US waves by the skull, and low efficacy in hypoxic tumor regions. The development of nanosonosensitizers is an effective solution to these problems. Designer nanosonosensitizers provide significantly improved targeting, tumor enrichment, and enhanced therapeutic efficacy through more effective optimization of their physicochemical characteristics and incorporation of responsive designs. Herein, the application of SDT in GBM, its limitations and the ways to overcome them, including the combination of SDT and other modalities of treatment, such as chemotherapy, immunotherapy, and targeted gene therapy using nanotechnology, are discussed. With the capability of nanoscience and US technology, these multimodal synergistic strategies hold great potential to enhance the treatment outcomes and the life quality of patients with GBM.
Yumeng Duan, S. Mo, Yunxue Xu· Nanoscale· 0 citations
Brain metastasis originating from breast cancer is an uncommon but clinically significant complication that poses substantial therapeutic challenges and is associated with poor patient prognosis. Traditional treatment modalities-including surgical resection, whole-brain radiation therapy, stereotactic radiosurgery, and systemic chemotherapy-often fail to achieve satisfactory long-term control due to the protective nature of the blood-brain barrier (BBB), tumor heterogeneity, and the aggressive biology of metastatic lesions. This comprehensive review delves into recent advances in modern therapeutic approaches that aim to enhance the efficacy of conventional treatments for rare brain metastases from breast cancer (BC). We systematically evaluate emerging strategies such as advanced drug delivery technologies, including nanoparticles (NPs), polymeric NPs, and liposomal formulations, which are designed to overcome pharmacokinetic limitations and improve the penetration and retention of chemotherapeutic agents within the central nervous system (CNS). The review also explores the integration of immunotherapies, particularly immune checkpoint inhibitors and adoptive cell therapies-with traditional modalities to potentiate antitumor immune responses in the brain microenvironment. Moreover, we discuss the development and application of novel radiosensitizers and combination regimens aimed at overcoming the inherent and acquired radioresistance of metastatic tumors. The synthesis of current preclinical models and clinical trial data provides critical insights into the potential of these combined approaches to enhance patient survival and quality of life. Finally, we identify key challenges, including the need for personalized treatment protocols and the management of therapy-related toxicities, and propose future directions for research.
Ghazala Muteeb, Aya Y El-Sayed, Mohamed S. AboHoussien et al.· SLAS discovery : advancing l...· 0 citations
Glioblastoma remains the most aggressive primary malignant brain tumor in adults, with survival largely unchanged despite advances in molecular diagnostics and supportive care. Therapeutic failure reflects fundamental biological and anatomical barriers, including intratumoral heterogeneity, an immunosuppressive tumor microenvironment, and restricted drug delivery across the blood-brain barrier. In this Review, we summarize the current standard of care and critically examine emerging strategies aimed at overcoming these constraints, including locoregional delivery technologies, immunotherapy, biomarker-defined precision approaches, and adaptive clinical trial designs. We highlight key translational and clinical studies shaping the field and discuss principles for developing more effective, integrated therapeutic paradigms.
Genaro R. Villa, Ashish D. Patel, D. Reardon et al.· Science Translational Medici...· 0 citations
A narrative review comprehensively summarizes the advances achieved between 2016 and 2026 in GBM-directed gene therapy, focusing on the engineering principles, biological characteristics, and translational applications of viral vectors including retroviral, adenoviral, and adeno-associated viral systems.
Alper Demirezen, Sumeyye Seher Karaman· International Journal of Med...· 0 citations
