temozolomide

Compared to temozolomide (TMZ), PLB more potently inhibited the viability of PDFS cells...The mechanism involves suppression of the Nrf2/FTH1 pathway, subsequent upregulation of NCOA4, and ferritinophagy-driven iron overload. These results identify PLB as a potential ferroptosis inducer and warrant further investigation into its therapeutic potential for NFPA.

P3, N=450, Active, not recruiting, Ivy Brain Tumor Center | Recruiting --> Active, not recruiting

Proteomics analysis revealed a strategic mechanism to resist TMZ-induced apoptosis by upregulating exosomal proteins associated with biogenesis, chemoresistance, and therapeutic adaption. This finding revealed a considerable TMZ resistance mechanism and provided a new inspiration for preventing exosome biogenesis to resensitise TMZ cytotoxicity towards GBM.

Drug testing with temozolomide (TMZ) demonstrated reduced sensitivity under hypoxic conditions, shown by a 56% increase in IC50, reflecting clinically relevant therapy resistance. These findings show the ability of the model to mimic key properties of the GBM microenvironment at both phenotypic and molecular levels and offer a physiologically relevant platform to study GBM biology and evaluate therapeutic responses.

PRONano is brain-targeted, rationally designed nanoformulation which can overcome major A1874 delivery constraints. This strategy augmented PROTAC delivery and therapeutic potential in GBM, supporting future preclinical development.

Finally, we evaluate therapeutic strategies that combine ferroptosis modulation with radiotherapy, temozolomide chemotherapy, immunotherapy, and nanomedicine-based delivery. We propose that ferroptosis-targeted strategies in GBM should be guided by tumor context, immune-cell preservation, and biomarker-based patient stratification.

High ALKBH2 expression in chemotherapy-treated IDH-wild-type glioma and low LMO7 expression in the CGGA astrocytoma cohort are each associated with shorter overall survival. Together, these results indicate that oxidative stress-coupled LMO7-dependent polyubiquitination of ALKBH2 modulates TMZ sensitivity in GBM, particularly in MGMT-deficient tumors.

Collectively, our findings strongly suggest that BA-101 has potential for further preclinical and translational development as an anticancer agent and a novel TMZ chemosensitizer for GBM therapy.

P=N/A, N=100, Recruiting, NanoAlvand

These coordinated pathways drive an "angiogenic switch," facilitate "metabolic migration," and induce significant resistance to chemotherapies, including gemcitabine and temozolomide. The hypoxamir-TAM axis is a fundamental driver of immune evasion and therapeutic failure. Targeting this dual-axis framework offers a viable strategy for restoring anti-tumor immunity, while circulating hypoxamirs represent high-value liquid biopsy biomarkers for real-time TME monitoring.

ECM stiffening is linked to stemness maintenance and temozolomide resistance in recurrent GBM through H3K18la-associated epigenetic regulation, while ITGA4/YAP-related mechanosensing provides a membrane-proximal axis that can be attenuated by multivalent VCAM1-Fc. Multivalent VCAM1-Fc may therefore reduce stiffness-associated malignant phenotypes by limiting ITGA4-dependent mechanotransduction.

P2, N=78, Recruiting, University of Zurich | Not yet recruiting --> Recruiting | Initiation date: Dec 2025 --> Jun 2026