%0 Journal Article
%A D Azorín, Daniel
%A Hoffmann, Dirk Carsten Frieder
%A Hebach, Nils
%A Jung, Erik
%A Hausmann, David
%A Ratliff, Miriam
%A Hai, Ling
%A Horschitz, Sandra
%A Jabali, Ammar
%A Osswald, Matthias
%A Karreman, Matthia Andrea
%A Kessler, Tobias
%A Wendler, Susann
%A Mayer, Chanté Desiree
%A Löb, Cathrin
%A Lehnert, Pascal
%A Cebulla, Gina Marie
%A Reibold, Denise
%A Khajuria, Rajiv
%A Bordignon, Pino
%A Moor, Andreas E
%A Holland-Letz, Tim
%A Reckless, Jill
%A Ramsden, Nigel
%A Grainger, David
%A Kreshuk, Anna
%A Koch, Philipp
%A Wick, Wolfgang
%A Heuer, Sophie
%A Winkler, Frank
%T Screening for Tumor Microtube-Targeting Drugs Identifies PKC Modulators as Multipotent Inhibitors of Glioblastoma Progression.
%J Cancer discovery
%V nn
%@ 2159-8274
%C Philadelphia, Pa.
%I [Verlag nicht ermittelbar]
%M DKFZ-2025-02075
%P nn
%D 2025
%Z #EA:B320#LA:B320# / epub
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41065276
%R 10.1158/2159-8290.CD-24-0414
%U https://inrepo02.dkfz.de/record/305229