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| Home > Publications database > Screening for Tumor Microtube-Targeting Drugs Identifies PKC Modulators as Multipotent Inhibitors of Glioblastoma Progression. |
| Home > Publications database > Screening for Tumor Microtube-Targeting Drugs Identifies PKC Modulators as Multipotent Inhibitors of Glioblastoma Progression. |
| Journal Article | DKFZ-2025-02075 |
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2025
[Verlag nicht ermittelbar]
Philadelphia, Pa.
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Please use a persistent id in citations: doi:10.1158/2159-8290.CD-24-0414
Abstract: Glioblastomas are incurable primary brain tumors that depend on neural-like cellular processes, tumor microtubes (TMs), to invade the brain. TMs also interconnect single tumor cells to a communicating multicellular network that resists current therapies. Here, we developed a combined, comprehensive in vitro/in vivo anti-TM drug screening approach, including machine-learning-based analysis tools. Two Protein Kinase C (PKC) modulators robustly inhibited TM formation and pacemaker tumor cell-driven, TM-mediated glioblastoma cell network communication. Since TM-unconnected tumor cells exhibited increased sensitivity to cytotoxic therapy, the PKC activator TPPB was combined with radiotherapy, and long-term intravital 2-photon microscopy paired with spatially resolved multiomics revealed anti-TM and anti-tumor effects. TPPB treatment also decreased the expression of tweety family member 1 (TTYH1), a key driver of invasive TMs. Our study establishes a novel screening pipeline for anti-TM drug development, identifies a TM master regulator pathway, and supports the approach of TM targeting for efficient brain tumor therapies.
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