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000305229 1001_ $$00000-0002-0002-4307$$aD Azorín, Daniel$$b0$$eFirst author
000305229 245__ $$aScreening for Tumor Microtube-Targeting Drugs Identifies PKC Modulators as Multipotent Inhibitors of Glioblastoma Progression.
000305229 260__ $$aPhiladelphia, Pa.$$b[Verlag nicht ermittelbar]$$c2025
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000305229 520__ $$aGlioblastomas are incurable primary brain tumors that depend on neural-like cellular processes, tumor microtubes (TMs), to invade the brain. TMs also interconnect single tumor cells to a communicating multicellular network that resists current therapies. Here, we developed a combined, comprehensive in vitro/in vivo anti-TM drug screening approach, including machine-learning-based analysis tools. Two Protein Kinase C (PKC) modulators robustly inhibited TM formation and pacemaker tumor cell-driven, TM-mediated glioblastoma cell network communication. Since TM-unconnected tumor cells exhibited increased sensitivity to cytotoxic therapy, the PKC activator TPPB was combined with radiotherapy, and long-term intravital 2-photon microscopy paired with spatially resolved multiomics revealed anti-TM and anti-tumor effects. TPPB treatment also decreased the expression of tweety family member 1 (TTYH1), a key driver of invasive TMs. Our study establishes a novel screening pipeline for anti-TM drug development, identifies a TM master regulator pathway, and supports the approach of TM targeting for efficient brain tumor therapies.
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000305229 7001_ $$0P:(DE-He78)e50ff195896914d35f54ed1bf913e270$$aHoffmann, Dirk Carsten Frieder$$b1$$eFirst author$$udkfz
000305229 7001_ $$0P:(DE-He78)5319a1b2dfba3c45ea5b99634da32bf9$$aHebach, Nils$$b2$$udkfz
000305229 7001_ $$0P:(DE-He78)bb545561110f9a827ab21f8586566205$$aJung, Erik$$b3
000305229 7001_ $$0P:(DE-He78)b560411dc6b7b16b688355a5f0cb08f8$$aHausmann, David$$b4$$udkfz
000305229 7001_ $$0P:(DE-He78)ce9cbc0fcc94b04884d88105f812ed01$$aRatliff, Miriam$$b5$$udkfz
000305229 7001_ $$0P:(DE-He78)7cde365fa8f836be201c050de81e7a03$$aHai, Ling$$b6
000305229 7001_ $$aHorschitz, Sandra$$b7
000305229 7001_ $$00000-0002-2772-8531$$aJabali, Ammar$$b8
000305229 7001_ $$0P:(DE-He78)e5e541194cff586d79a62f992420e0c5$$aOsswald, Matthias$$b9
000305229 7001_ $$0P:(DE-He78)85fdf4bdb0f779fa0bda00b41c9f8a8f$$aKarreman, Matthia Andrea$$b10$$udkfz
000305229 7001_ $$0P:(DE-He78)5c2c9cbe6ce72553684d82d94aebdadd$$aKessler, Tobias$$b11$$udkfz
000305229 7001_ $$0P:(DE-He78)3fcbd3ecdb47b9f8187ce0c6d52be0ac$$aWendler, Susann$$b12$$udkfz
000305229 7001_ $$0P:(DE-He78)2b9db23b1b7219332b431c083dce6480$$aMayer, Chanté Desiree$$b13$$udkfz
000305229 7001_ $$0P:(DE-He78)45a91db2cc610488a7d7547589d1eb22$$aLöb, Cathrin$$b14
000305229 7001_ $$0P:(DE-He78)f454c105dbecd13fd47fc42e9e11f560$$aLehnert, Pascal$$b15$$udkfz
000305229 7001_ $$0P:(DE-He78)6f03d3271fd11bb3dc3efca8a16f0cbb$$aCebulla, Gina Marie$$b16$$udkfz
000305229 7001_ $$0P:(DE-He78)fa7f7d7870419d5952e598216bf0a2ee$$aReibold, Denise$$b17$$udkfz
000305229 7001_ $$0P:(DE-He78)4fed0ad4b12b9a9335ff08edd28ddf6f$$aKhajuria, Rajiv$$b18
000305229 7001_ $$00000-0002-3157-8695$$aBordignon, Pino$$b19
000305229 7001_ $$00000-0001-8715-8449$$aMoor, Andreas E$$b20
000305229 7001_ $$0P:(DE-He78)457c042884c901eb0a02c18bb1d30103$$aHolland-Letz, Tim$$b21$$udkfz
000305229 7001_ $$00009-0004-4658-095X$$aReckless, Jill$$b22
000305229 7001_ $$00009-0001-6020-1184$$aRamsden, Nigel$$b23
000305229 7001_ $$00000-0002-3211-2045$$aGrainger, David$$b24
000305229 7001_ $$00000-0003-1334-6388$$aKreshuk, Anna$$b25
000305229 7001_ $$aKoch, Philipp$$b26
000305229 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b27$$udkfz
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000305229 7001_ $$0P:(DE-He78)6c294453ee36ad59deddc5494fa6aa4b$$aWinkler, Frank$$b29$$eLast author$$udkfz
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