Aug 2026· Nature Reviews Clinical Oncology· 0 citations· 198 references
Medicine
TL;DR
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.
A narrative review summarizes the major signaling pathways implicated in GBM pathogenesis, including EGFR, PI3K/AKT/mTOR, Wnt, and TGF-β signaling, while also discussing emerging therapeutic targets such as FGFR3–TACC3 fusions, regorafenib, and natural killer cell-based immunotherapy.
William W Li, J. Chen, Yiying Ma· Future Science OA· 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
Glioblastoma (GBM) is an intricate intracranial tumor that has cataclysmic outlook. It originates from glial cells having an average life expectancy of one and a half years. Despite intensive multimodal therapy, the tumor's innate invasiveness and cellular heterogeneity lead to nearly inevitable recurrence. Recent advancements have shifted the focus toward the interplay between genetic drivers and the dynamic epigenetic landscape. WHO classification defined GBM as an IDH-wildtype tumor, distinguishing it from IDH-mutant. Present review explores the complex epigenetic mechanisms such as DNA methylation, histone modification and RNA editing that drive GBM progression, shape the tumor microenvironment and facilitate immune evasion. The review further discusses severe translational barriers, including blood brain barrier penetrance, tumor heterogeneity, and the immunosuppressive effects of steroids. Finally, we highlight the therapeutic potential of targeting these epigenetic vulnerabilities through inhibitors of histone deacetylase and DNA methyltransferase, either alone or combined with modern immunotherapies to overcome treatment resistance and improve patient outcomes.
The mechanisms through which glioblastoma is initiated, localized, and eludes therapy responses are summarized and an update is provided on recent advances made within this therapeutic space to overcome GBM‐mediated immunosuppression.
Emerson Achari, Farah Ahmady-Nield, Amit Sharma et al.· Immunology and Cell Biology· 0 citations
This comprehensive review highlights BMBC resistance mechanisms, drawing from preclinical models, clinical studies, and genomic analyses, and highlights the potential for personalized, multi-targeted approaches to improve patient outcomes in BMBC.
Paromita Sarker, Shreyas S Rao· Biochimica et biophysica act...· 0 citations
Glioblastoma (GBM) remains one of the most lethal brain malignancies, characterized by aggressive invasion, therapeutic resistance and poor prognosis. Conventional treatment approaches are limited by systemic toxicity, poor blood–brain barrier (BBB) penetration and lack of tumor specificity. Nanoparticle-based therapeutics offer a transformative paradigm redefining drug delivery, diagnostics and multimodal strategies in GBM. In this review, we critically explore a diverse variety of advanced nanocarrier platforms designed for anti-proliferative, radiosensitizing and immunomodulatory interventions. These systems enhance BBB penetration, tumor localization and enable co-delivery of chemotherapeutics, gene therapies and imaging agents with high precision. Innovative approaches show efficacy against glioma stem cells, modulate the tumor microenvironment and address resistance mechanisms. Integration with radiotherapy and immunotherapy yields synergistic tumor suppression and immune activation, advancing personalized nanomedicine. Despite these advancements, translational hurdles remain nanogenotoxicity, long-term biosafety, immune responses and regulatory barriers. This review emphasizes such challenges while identifying opportunities for strategic innovation in GBM nanotherapy. By uniquely bridging preclinical advances with emerging clinical perspectives, we highlight its distinct contribution within the field. By bridging nanotechnology, molecular oncology and bioengineering, we highlight how rational nanoparticle design can shift GBM management toward targeted, multimodal precision therapy, offering renewed hope against one of oncology’s most intractable diseases.
Keywords: Glioblastoma, Nanoparticles, Blood-Brain Barrier, Nanotechnology, Nanomedicine, Nanotherapeutics.
