Animal studyReported positivePreclinical onlyTier 2 · animal
Advanced materials (Deerfield Beach, Fla.) · Jan 2026
glioblastoma
The authors developed innate immune-stimulating nanoparticles (INSTNA) carrying an iridium-based mitochondrial-targeting complex (Ir-mito) and siRNA against MCJ to impair mitochondrial respiration in glioblastoma cells. In cell experiments and a postoperative GBM mouse model, INSTNA induced mitochondrial oxidative phosphorylation stress and mitochondrial matrix release, remodeled the immunosuppressive tumor microenvironment, and produced pronounced tumor regression when delivered in a hydrogel and combined with tumor-treating fields. The study reports enhanced innate and adaptive immune activation associated with these effects. No human data are reported in the abstract.
Studied with: tumor-treating fields, hydrogel-mediated delivery.
Key findings
- INSTNA encapsulating Ir-mito and si-MCJ disrupt mitochondrial function of GBM cells.
- The engineered charge-reversal INSTNA impair the mitochondrial electron transport chain, inducing OXPHOS stress and mitochondrial matrix release.
- Combination with tumor-treating fields enhanced the disruption of mitochondrial function.
- Hydrogel-mediated delivery of INSTNA in a postoperative GBM mouse model significantly remodeled the immunosuppressive microenvironment.
- Treatment resulted in pronounced tumor regression and potentiation of innate and adaptive immune responses in the mouse model.
Limitations: Preclinical study using in vitro experiments and a mouse (postoperative GBM) model only; no human data reported.; Abstract does not report sample sizes, randomization, or control group details.; Safety, toxicity, and long-term outcomes are not reported in the abstract.; Quantitative effect sizes, statistical values, and detailed methods are not provided in the abstract..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed
ReviewMechanismMixed resultsLimited evidenceTier 4 · clinical
Cancers · Dec 2025
glioblastoma
This review summarizes current knowledge about circulating tumor cells (CTCs) in glioblastoma, describing their unique properties, detection technologies, and the challenges of rarity, lack of epithelial markers, and the blood-brain barrier. It discusses potential uses of CTC analysis for assessing tumor heterogeneity, monitoring treatment response, detecting minimal residual disease and early relapse, and reviews preclinical mouse models (cell-line xenografts, patient-derived xenografts, genetically engineered mouse models) and their limitations.
Key findings
- CTCs have been detected in glioblastoma, challenging the traditional view of GBM as non-metastatic.
- Glioblastoma CTCs are rare, lack epithelial markers, and are affected by the blood-brain barrier, requiring specialized enrichment approaches.
- CTC analysis in glioblastoma may provide information on tumor heterogeneity, treatment response, and minimal residual disease.
- Emerging clinical studies are using CTCs for early relapse detection and therapy monitoring.
- Preclinical mouse models for glioblastoma include cell-line xenografts, patient-derived xenografts (PDX), and genetically engineered mouse models (GEMMs), each with advantages and limitations.
- PDX models retain genetic and histological features of primary tumors but cannot fully recapitulate human antitumor immunity; GEMMs allow study of specific genetic alterations but may lack intratumoral heterogeneity.
Limitations: This is a review article and does not present new primary experimental data.; CTCs in glioblastoma are rare and lack epithelial markers, which complicates detection and analysis.; The blood-brain barrier presents a challenge for CTC detection and interpretation.; Preclinical models discussed have known limitations: PDX models do not reflect human antitumor immunity and GEMMs may not capture intratumoral heterogeneity.; Clinical evidence is described as emerging, implying early-stage or limited-size clinical studies rather than definitive clinical validation..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismInconclusiveLimited evidenceTier 3 · early human
Cancer cell · Dec 2025 · spatial profiling of glioblastoma specimens
glioblastoma
The authors spatially profiled human glioblastoma specimens. They report uncovering cellular mechanisms that govern the extent of gene expression heterogeneity in malignant cells.
Key findings
- The study performed spatial profiling of glioblastoma specimens.
- The authors uncovered cellular mechanisms that govern the extent of gene expression heterogeneity in malignant cells.
Limitations: Abstract provides no sample size or details on patient cohorts.; Only descriptive spatial profiling of specimens is reported in the abstract; no therapeutic intervention or clinical trial data.; The abstract does not provide mechanistic details, validation experiments, or quantitative results..
AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed
ReviewMechanismReported positivePreclinical onlyTier 1 · lab
Cancer cell · Nov 2025
glioblastoma
This Cancer Cell piece summarizes work by Yang et al. showing that glioblastoma co-opts cholinergic neural circuits. The authors describe mechanisms by which the tumor exploits cholinergic signaling to disrupt the hierarchical organization of brain networks and note that these findings change how we think about tumor–brain interactions and suggest potential therapeutic directions.
Key findings
- Glioblastoma alters normal brain function by hijacking neural circuits.
- Yang et al. elucidate mechanisms by which glioblastoma exploits cholinergic signaling pathways.
- This hijacking disrupts the hierarchical organization of brain networks.
- The analysis reframes tumor–brain interactions and is said to open new therapeutic avenues.
Limitations: Abstract is a short commentary/review and provides no experimental details or methods.; No species, model system, sample sizes, or quantitative results are reported in the abstract.; Unable to assess primary data, study design, or statistical strength from this abstract alone..
AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed
Animal studyMechanismReported positivePreclinical onlyTier 2 · animal
Trends in pharmacological sciences · Nov 2025 · commentary/review of a study
glioblastomabrain neoplasms
This article discusses a study in glioblastoma showing that tumor cells took up more serine. It also reports that limiting serine uptake made chemoradiation work better in preclinical models. The abstract is mainly a commentary on emerging research rather than a full original trial report.
Studied with: chemoradiation.
Key findings
- Tumor metabolism in glioblastoma patients showed increased import of serine.
- Limiting serine uptake enhanced the effectiveness of chemoradiation in preclinical models of glioblastoma.
Limitations: This is not a full original study report; it is a commentary/review-style article.; The abstract does not provide methods, sample size, or quantitative results.; The sensitization finding is preclinical, so human clinical benefit is unproven..
Discusses a metabolic vulnerability in glioblastoma and preclinical chemoradiation sensitization.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early human
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · Oct 2025
glioblastoma
The authors analyzed blood, tumor cells, and plasma-derived extracellular vesicles from glioblastoma patients and healthy donors to assess how Tumor Treating Fields (TTFields) affect coagulation-related biology. They report that short-term TTFields exposure prolonged blood coagulation and reduced clot rigidity by decreasing Factor II/FXIII activity and platelet count, while patient-derived GBM cells showed increased tissue factor (TF) abundance and changes in coagulation-related gene expression. Co-culture experiments indicated TTFields modulate pro- and anticoagulant factors and inflammatory pathways in the tumor microenvironment. The study does not report quantitative sample sizes or clinical thromboembolic outcomes.
Studied with: radiochemotherapy.
Key findings
- Short-term TTFields exposure significantly prolongs blood coagulation in GBM patients and healthy donors by altering tissue factor (TF) expression and disrupting the extrinsic coagulation pathway.
- TTFields reduced clot rigidity by decreasing Factor II/FXIII activity and platelet count, without impairing fibrinogen function.
- Patient-derived GBM cells exposed to TTFields exhibited increased TF abundance.
- RNA microarray of GBM cells after TTFields exposure showed upregulation of platelet adhesion marker ITGA2 and downregulation of THBS1.
- TXNIP, described as a coagulation-modulating gene linked to immune regulation, was downregulated after TTFields exposure.
- In an allogeneic co-culture model of patient-derived GBM cells and peripheral blood, TTFields modulated coagulation and immune responses, suggesting rebalancing of pro- and anticoagulant factors and alteration of inflammatory pathways.
Limitations: No sample size or detailed patient cohort characteristics are reported in the abstract.; Study reports short-term exposure effects; duration and long-term consequences are not defined.; Observational and ex vivo/in vitro analyses; causality in patients in vivo is not established.; No clinical outcome data on thromboembolic events or patient-level clinical endpoints are provided.; Findings include mixed pro- and anticoagulant signals (e.g., increased TF in tumor cells vs prolonged blood coagulation), complicating interpretation..
AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human trialTrialReported positiveModerate evidenceTier 4 · clinicaln = 31
Med (New York, N.Y.) · Sep 2025 · Phase 2, single-arm with case-matched control comparison
This phase 2 clinical trial enrolled 31 patients with newly diagnosed glioblastoma after chemoradiation to test adding pembrolizumab to TTFields plus temozolomide. Among 26 patients treated per protocol, median progression-free survival was 12.0 vs. 5.8 months (HR 0.377; p = 0.0026) and median overall survival was 24.8 vs. 14.6 months (HR 0.522; p = 0.0477) compared to case-matched controls. Patients who had biopsy only showed larger PFS and OS benefits than those with maximal resection. Immune analyses suggested TTFields induced a T1IFN-driven clonal T cell expansion while pembrolizumab supported adaptive replacement and sustained T cell activation; severe treatment-related adverse events were reported as 7.5%.
Reported effects: median PFS 12 mo · PFS hazard ratio 0.377 [0.217–0.653], p=0.0026 · +7 more
Studied with: pembrolizumab, temozolomide.
Key findings
- Among 26 patients treated per protocol, median PFS was 12.0 vs. 5.8 months in controls (HR 0.377, 95% CI 0.217-0.653; p = 0.0026).
- Among 26 patients treated per protocol, median OS was 24.8 vs. 14.6 months in controls (HR 0.522, 95% CI 0.301-0.905; p = 0.0477).
- Patients undergoing biopsy had longer PFS (27.2 vs. 9.6 months; HR 0.37, 95% CI 0.16-0.85; p = 0.014) and OS (31.6 vs. 18.8 months; HR 0.4, 95% CI 0.17-0.92; p = 0.023) compared to maximal resection.
- Severe adverse events constituted 7.5% of treatment-related toxicities.
- Immune correlates: TTFields promoted clonal T cell expansion via a T1IFN-driven trajectory, while pembrolizumab supported adaptive replacement of these clones, sustaining T cell activation and memory formation, especially in biopsy-only patients.
Limitations: Small sample size (31 enrolled; 26 treated per protocol).; Phase 2, non-randomized, single-arm design with case-matched controls rather than a randomized control group.; Potential selection or matching biases inherent to case-matched control comparisons.; Follow-up duration not specified in the abstract.; Funded by Novocure (industry support) which may present a conflict of interest..
AI summary of the abstract, published automatically under the strong-evidence tier · Jul 2026; an editor has not yet reviewed it. Describes what this study reported, not medical advice. View on PubMed
ReviewReported positiveModerate evidenceTier 4 · clinical
Expert review of medical devices · Sep 2025 · review
glioblastomabrain neoplasms
This review summarizes tumor treating fields (TTFields), an alternating electric-field therapy for glioblastoma that uses dielectrophoresis to disrupt mitosis in dividing cells. The authors state that clinical trials have shown TTFields added to standard adjuvant treatments significantly improved progression-free and overall survival. They also note unresolved questions about neuropsychological effects and management of postoperative motor deficits and call for further research.
Studied with: standard adjuvant treatments.
Key findings
- TTFields therapy applies alternating electric fields and, via dielectrophoresis, selectively disrupts mitotic processes in replicating cells.
- Clinical trials reported that TTFields significantly improved progression-free and overall survival rates when combined with standard adjuvant treatments.
- Unanswered questions remain about the impact of TTFields on neuropsychological functioning and the management of postoperative motor deficits.
Limitations: This publication is a review rather than primary clinical trial data.; The abstract provides no numeric trial results or detailed quantitative outcomes.; The review notes unresolved clinical questions (neuropsychological effects, motor deficit management), indicating incomplete evidence.; Safety and long-term outcome details are not provided in the abstract..
AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed