SynthesisCancer chemotherapy and pharmacology2026
Therapeutic modulation of the blood-brain barrier in brain tumors: a systematic review of clinical and translational approaches.
Synthesis in Cancer chemotherapy and pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
5 authors.
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Abstract
purposeThe blood–brain barrier (BBB) is a major obstacle to effective treatment in neuro-oncology, as it limits the penetration of therapeutic agents into tumors of the central nervous system. This systematic review aimed to systematically synthesize clinical and translational evidence on BBB modulation for enhanced drug delivery in brain tumor therapy, with emphasis on clinical outcomes, intratumoral exposure and mechanistic pharmacodynamic endpoints.
methodsA systematic search was conducted in PubMed and ScienceDirect from January 2000 to December 2025, following PRISMA guidelines. We included clinical and translational research, such as randomized controlled trials, cohort studies, and case series, that assessed techniques to disrupt the blood–brain or blood–tumor barrier. Main strategies included intra-arterial osmotic disruption, low-intensity focused ultrasound, laser interstitial thermal therapy, pharmacological modulation, and nanotechnology-based delivery systems. Efficacy, safety, and pharmacokinetics were evaluated.
resultsTwenty-five studies were included. Osmotic disruption with intra-arterial mannitol remains the most studied approach, showing enhanced intratumoral drug concentration and potential survival benefits. Focused ultrasound has emerged as a non-invasive, repeatable method with immunomodulatory effects. Laser interstitial therapy facilitates temporary barrier disruption. Pharmacological agents like AZD1775 and Trotabresib, and targeted systems such as immunoliposomes, showed variable central nervous system penetration. Biomarkers and imaging parameters, such as transthyretin and Ktrans, were used to assess barrier permeability.
conclusionTherapeutic disruption of the blood–brain barrier is a promising strategy to enhance intratumoral drug delivery in brain tumors. Further clinical trials and biomarker validation are needed to optimize safety and efficacy.
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