Glioblastoma (GBM) remains one of the deadliest brain cancers, with limited advancements in treatments over the past 30 years. Current therapies have not significantly improved survival rates, necessitating new therapeutic strategies. In this regard, ion channels, increasingly implicated in tumorigenesis, represent a potential target for drug repurposing due to the availability of numerous approved ion channel inhibitors that can penetrate the blood-brain barrier.

A recent study explored this potential by screening 72 ion channel modulators against patient-derived GBM cells, revealing that DPI-201-106, a voltage-gated sodium channel modulator, significantly reduced glioblastoma cell viability by inducing cell cycle arrest and apoptosis. The study highlighted its synergistic potential when combined with DNA damage response inhibitors, specifically the CHK1 inhibitor prexasertib and the PARP inhibitor niraparib.

Using the Patchliner automated patch clamp system, the researchers confirmed that DPI-201-106 has on-target effects in GBM cells by modulating voltage-gated sodium channel currents and reducing the peak inward sodium current.

In GBM xenograft models, combination treatments extended survival significantly, particularly DPI-201-106 and prexasertib, which added 20 days to median survival compared to monotherapies.

Furthermore, DPI-201-106 demonstrated efficacy beyond glioblastoma, showing promise as a single agent in medulloblastoma and ependymoma cells, and as a combination therapy in a pediatric diffuse midline glioma model, indicating that DPI-201-106 may be a suitable treatment to explore across a range of brain tumors for adults and children.

These findings highlight the potential of repurposing existing ion channel modulators in combination with DNA damage response inhibitors as a novel treatment strategy for glioblastoma.

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Find the full article here: Ion channel modulator DPI-201-106 significantly enhances anti-tumour activity of DNA damage response inhibitors in glioblastoma

Learn more about the Patchliner, the most versatile automated patch clamp system on the market: https://www.nanion.de/products/patchliner/