TY  - JOUR
AU  - D Azorín, Daniel
AU  - Hoffmann, Dirk Carsten Frieder
AU  - Hebach, Nils
AU  - Jung, Erik
AU  - Hausmann, David
AU  - Ratliff, Miriam
AU  - Hai, Ling
AU  - Horschitz, Sandra
AU  - Jabali, Ammar
AU  - Osswald, Matthias
AU  - Karreman, Matthia Andrea
AU  - Kessler, Tobias
AU  - Wendler, Susann
AU  - Mayer, Chanté Desiree
AU  - Löb, Cathrin
AU  - Lehnert, Pascal
AU  - Cebulla, Gina Marie
AU  - Reibold, Denise
AU  - Khajuria, Rajiv
AU  - Bordignon, Pino
AU  - Moor, Andreas E
AU  - Holland-Letz, Tim
AU  - Reckless, Jill
AU  - Ramsden, Nigel
AU  - Grainger, David
AU  - Kreshuk, Anna
AU  - Koch, Philipp
AU  - Wick, Wolfgang
AU  - Heuer, Sophie
AU  - Winkler, Frank
TI  - Screening for Tumor Microtube-Targeting Drugs Identifies PKC Modulators as Multipotent Inhibitors of Glioblastoma Progression.
JO  - Cancer discovery
VL  - nn
SN  - 2159-8274
CY  - Philadelphia, Pa.
PB  - [Verlag nicht ermittelbar]
M1  - DKFZ-2025-02075
SP  - nn
PY  - 2025
N1  - #EA:B320#LA:B320# / epub
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:41065276
DO  - DOI:10.1158/2159-8290.CD-24-0414
UR  - https://inrepo02.dkfz.de/record/305229
ER  -