Glioblastoma remains one of the most aggressive and treatment-resistant brain tumors. One key challenge in its treatment is the presence of so-called cancer stem cells, which are thought to drive tumor recurrence and poor prognosis. Prof. Kahlert and his team—renowned experts in cancer stem cell biology—utilized advanced glioblastoma spheroid models representing the mesenchymal transcriptional subtype to assess THP’s anti-proliferative activity. A wide range of in vitro assays confirmed THP's ability to inhibit cancer cell growth.

Moreover, transcriptomic profiling of treated glioblastoma cells revealed significant changes in gene expression and metabolic signaling pathways, suggesting possible molecular mechanisms behind the drug's action.

Encouraging results were also seen in in vivo experiments coordinated by EPO Berlin-Buch, using patient-derived xenograft (PDX) models with mesenchymal glioblastoma stem cells engrafted into the brains of immunocompromised mice. In some cases, THP treatment led to a measurable response, highlighting its therapeutic potential.

Importantly, this study aligns with recent advances in neurotransmitter signaling in glioblastoma (see Vargas-Toscano et al., 2020a; Venkataramani et al., 2019), suggesting that THP may interfere with synaptic-like connections between neurons and tumor cells, offering a novel therapeutic angle.

This project is part of a long-term partnership aimed at building a pan-cancer in vitro and in vivo modeling platform for difficult-to-treat cancers, not only within the CNS but also including pancreatic cancer (PDAC), esophageal squamous cell carcinoma (ESSC), and secondary tumors of the prostate. Stay tuned for more updates from this exciting and rapidly evolving collaboration. Kahlert will also present at upcoming EPO Spring meeting in June in Berlin.