30 A new research perspective published in Volume 13 of Oncoscience on 17th September 2026 reviews emerging treatments being investigated for Glioblastoma Multiforme (GBM), including agents in active and recently completed clinical trials. Titled “Emerging pharmacological agents for glioblastoma multiforme: An update on active clinical trials (2025–2026),” the perspective examines four major areas of research: molecular targeted therapies; immunotherapies and vaccines; oncolytic viruses and gene therapies; and treatments targeting tumour metabolism and the microenvironment. The perspective was led by first and corresponding author Mamunur Rahman from the Department of Pharmacy at East West University, Aftabnagar, Dhaka, Bangladesh. GBM is an aggressive primary brain tumour in adults, with a median overall survival of approximately 15 months despite surgery, radiotherapy, and temozolomide. Treatment remains difficult because GBM tumours can contain genetically and functionally diverse cancer cell populations. An immunosuppressive tumour microenvironment can limit effective anti-tumour immune responses, while the blood-brain barrier restricts many systemically administered drugs from reaching therapeutic concentrations within the tumour. Hypoxia and other features of the tumour environment can also contribute to treatment resistance. One major area of investigation is molecular targeted therapy. The review discusses approaches involving B7-H3, CDK4/6, the RAS/MAPK pathway, BRAF alterations, and other molecular vulnerabilities. Abemaciclib, a CDK4/6 inhibitor with relatively favourable brain penetration, is being investigated in combination with the ERK inhibitor LY3214996. Regorafenib, which inhibits multiple kinases involved in angiogenic and proliferative signalling, previously improved median overall survival compared with lomustine in the Phase 2 REGOMA trial for recurrent GBM, although it was also associated with more severe adverse events. The review highlights the growing importance of biomarker-guided patient selection. Molecular characteristics including MGMT promoter methylation, IDH mutation status, EGFR amplification, and BRAF V600E can help identify biologically distinct patient groups and guide enrolment in trials evaluating particular therapeutic strategies. This reflects a broader move away from treating GBM as a single uniform disease towards matching treatments with the molecular features of individual tumours. Immunotherapy is another major area of research. Dendritic cell vaccines are designed to expose the immune system to tumour-associated antigens and generate cytotoxic T-cell responses. The review discusses DCVax-L and other vaccine approaches, including the plasmid DNA vaccines INO-5401 and INO-9012 in combination with the PD-1 inhibitor cemiplimab. These strategies aim to generate immune responses against multiple tumour antigens while counteracting the profound immune suppression characteristic of GBM. CAR T-cell therapy is also being adapted to address the molecular heterogeneity of glioblastoma. Because tumour cells can lose individual target antigens, investigators are developing bivalent and multivalent CAR constructs capable of recognising more than one tumour-associated antigen. The perspective discusses a bivalent CAR T-cell strategy targeting EGFR and IL-13Rα2 in recurrent GBM, as well as engineered tumour-infiltrating lymphocytes designed to produce anti-PD-1 antibodies within tumours. Challenges include antigen loss, T-cell exhaustion, neurotoxicity, delivery route, and the immunosuppressive tumour microenvironment. Researchers are also exploring oncolytic and gene therapy platforms. Retroviral replicating vectors such as DB107-RRV/DB107-FC are designed to spread selectively through dividing tumour cells and convert a prodrug into a cytotoxic compound within the tumour. Other experimental gene therapy approaches seek to combine tumour-selective activity with immune stimulation. These strategies remain investigational and face challenges involving delivery, antiviral immunity, and the specialised infrastructure required for treatment. GBM’s altered metabolism provides another potential therapeutic target. The review describes agents such as BPM31510, which targets mitochondrial bioenergetics and redox homeostasis, and ASC40, an inhibitor of fatty acid synthase. Both are being evaluated in clinical trials, reflecting growing interest in disrupting the metabolic flexibility that allows GBM cells to survive under hypoxic and nutrient-limited conditions. Despite the expanding treatment pipeline, major barriers remain. Intratumoral heterogeneity can allow resistant cell populations to escape single-target treatments. Immunotherapies must overcome suppressive macrophages, myeloid-derived suppressor cells, regulatory T cells, and chronic T-cell exhaustion. Systemic agents must cross the blood-brain barrier, while tumour cells can adapt their metabolism in response to therapeutic pressure. Differences among clinical trials in eligibility criteria, endpoints, imaging assessments, and corticosteroid use also complicate comparisons between treatments. None of the emerging approaches reviewed has replaced the current temozolomide-based treatment paradigm. Instead, the evolving strategy is increasingly centred on biomarker-directed combinations, in which targeted, immune-based, or metabolic treatments are added for molecularly defined groups of patients. “The combination of precision molecular targeting with new immune activation methods and CNS based drug delivery and metabolic interference establishes a foundation for developing combination therapies which should use proven predictive biomarkers for maximum effectiveness.” Future progress may depend on adaptive clinical trial platforms that evaluate multiple therapies and molecular subgroups simultaneously, rational combinations that target several aspects of GBM biology, personalised neoantigen vaccines, and improved methods for delivering therapies across the blood-brain barrier. The authors also highlight emerging liquid biopsy and imaging biomarkers as potential tools for assessing treatment response. Overall, the perspective describes a GBM treatment landscape moving from broadly applied cytotoxic approaches towards mechanism-based, biomarker-guided, and combination strategies. Molecular targeting, immune activation, gene and oncolytic therapies, metabolic interventions, and improved CNS drug delivery are being investigated in parallel, but substantial biological and clinical obstacles remain. Results from ongoing Phase II and III studies will be critical for determining which approaches ultimately advance towards regulatory consideration.