% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Horschitz:300285,
      author       = {S. Horschitz$^*$ and A. Jabali and S. Heuer$^*$ and E.
                      Zillich and L. Zillich and D. C. Hoffmann$^*$ and A. S.
                      Kumar and D. Hausmann$^*$ and D. D. Azorin$^*$ and L.
                      Hai$^*$ and W. Wick$^*$ and F. Winkler$^*$ and P. Koch},
      title        = {{D}evelopment of a fully human
                      glioblastoma-in-brain-spheroid model for accelerated
                      translational research.},
      journal      = {Journal of advanced research},
      volume       = {nn},
      issn         = {2090-1232},
      address      = {Amsterdam ˜[u.a.]œ},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-00738},
      pages        = {nn},
      year         = {2025},
      note         = {#EA:A340# / epub},
      abstract     = {Glioblastoma (GBM) progression and therapeutic resistance
                      are significantly influenced by complex interactions between
                      tumor cells and the brain microenvironment, particularly
                      neurons. However, studying these interactions in
                      physiologically relevant conditions has remained challenging
                      due to limitations in existing model systems.Here, we
                      present hGliCS (human glioma-cortical spheroid), a novel
                      fully human brain tumor model that overcomes key limitations
                      of current approaches by combining patient-derived GBM cells
                      with mature human cortical neurons derived from induced
                      pluripotent stem cells.We demonstrate that GBM cells in
                      hGliCS develop three critical hallmark features observed in
                      patients: (i) formation of tumor microtubes enabling
                      intercellular communication, (ii) establishment of
                      neuron-glioma synapses, and (iii) development of an
                      interconnected network with coordinated calcium signaling.
                      Single-cell RNA sequencing reveals that tumor cells in
                      hGliCS exhibit cellular heterogeneity and transcriptional
                      profiles remarkably similar to those observed in mouse
                      xenografts, including activation of key oncogenic pathways
                      and neuronal-like features. Notably, while GBM cells showed
                      substantial transcriptional adaptation to the neural
                      environment, neurons maintained their core identity with
                      only subtle alterations in glutamate signaling and
                      structural gene expression. We validate hGliCS as a drug
                      screening platform by demonstrating resistance patterns to
                      standard chemotherapy and radiation similar to clinical
                      observations. Furthermore, we show the model's utility in
                      testing standard and novel therapeutic compounds targeting
                      cell proliferation and tumor-specific neurobiological
                      features, respectively.This physiologically relevant human
                      model system provides new opportunities for studying GBM
                      biology and tumor-neuron interactions in a controlled
                      environment. By bridging the gap between simplified in vitro
                      systems and complex in vivo models, hGliCS represents a
                      promising platform for therapeutic development and
                      personalized medicine approaches in GBM treatment.},
      keywords     = {Cancer treatment (Other) / Cortical spheroids (Other) /
                      Glioblastoma (Other) / Glioma heterogeneity (Other) /
                      Neuro-oncology (Other)},
      cin          = {A340 / B320 / HD01},
      ddc          = {500},
      cid          = {I:(DE-He78)A340-20160331 / I:(DE-He78)B320-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40188875},
      doi          = {10.1016/j.jare.2025.03.055},
      url          = {https://inrepo02.dkfz.de/record/300285},
}