gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

TTFields empowers the anti-glioblastoma activity of CUSP9v3 in vitro

TTFields führt zu einer Verstärkung der Aktivität von CUSP9v3 gegen Glioblastomzellen in vitro

Meeting Abstract

  • Qiyu Cao - Universitätsklinikum Ulm, Neurochirurgie, Ulm, Deutschland
  • Annika Dwucet - Universitätsklinikum Ulm, Neurochirurgie, Ulm, Deutschland
  • Richard Kast - IIAIGC Study Center, Burlington, VT, Vereinigte Staaten
  • Michal Hlavac - Universitätsklinikum Ulm, Neurochirurgie, Ulm, Deutschland
  • Mike-Andrew Westhoff - Universitätsklinikum Ulm, Kinder- und Jugendmedizin, Ulm, Deutschland
  • Markus David Siegelin - Columbia University, Department of Pathology and Cell Biology, New York, NY, Vereinigte Staaten
  • Christian Rainer Wirtz - Universitätsklinikum Ulm, Neurochirurgie, Ulm, Deutschland
  • Marc-Eric Halatsch - Cantonales Spital Winterthur, Neurochirurgie, Winterthur, Schweiz
  • presenting/speaker Georg Karpel-Massler - Universitätsklinikum Ulm, Neurochirurgie, Ulm, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocP159

doi: 10.3205/22dgnc472, urn:nbn:de:0183-22dgnc4725

Veröffentlicht: 25. Mai 2022

© 2022 Cao et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: Drug repurposing is a promising strategy to accelerate the clinical use of therapeutics with anti-neoplastic activity. In this study, we examined whether Tumor Treating Fields (TTFields) enhance the biological effects of the repurposed CUSP9v3 regimen in an in vitro setting of glioblastoma.

Methods: We performed MTT-assays to examine effects of the combination treatment on the viability of established, primary cultured and stem-like glioblastoma cells. Staining with annexin V/propidium iodide followed by flow cytometry was done to assess pro-apoptotic effects. Specific protein expression of members from the Bcl-2 family of proteins was determined by Western blot analyses.

Results: TTFields had at least additive anti-proliferative effects across established, primary cultured and stem-like glioblastoma cells when combined with CUSP9v3. In addition, flow cytometric analyses revealed that a simultaneous treatment with TTFields and CUSP9v3 significantly increased the fraction of annexin V-positive (apoptotic) glioblastoma cells. On the molecular level, the combination treatment led to a significant reduction of Bcl-2 levels.

Conclusion: These data suggest that TTFields enhance the susceptibility of glioblastoma cells towards CUSP9v3, potentially allowing significant dose reduction and decreased toxicity. TTFields are widely used for the treatment of glioblastoma patients and CUSP9v3 was recently shown to have a favorable safety profile in a phase Ib/IIa trial (NCT02770378) which facilitates transition of a combined approach to the clinical setting and warrants further investigation.