gms | German Medical Science

72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

Rapalink-1 Targets Glioblastoma Stem Cells and Acts Synergistically with Tumor Treating Fields to Reduce

Rapalink-1 zielt auf Glioblastom-Stammzellen ab und wirkt synergistisch mit Tumortherapiefelder, um die Resistenz gegen Temozolomid zu verringern

Meeting Abstract

  • presenting/speaker Andres Vargas-Toscano - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Ann-Christin Nickel - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Guanzhang Li - Beijing Neurosurgical Institute, Peking, China
  • Marcel A. Kamp - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Sajjad Muhammad - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Gabriel Leprivier - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Ellen Fritsche - Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Deutschland
  • Roger A. Barker - University of Cambridge, Department of Clinical Neurosciences and WT-MRC Stem Cell Institute, Cambridge, Vereinigtes Königreich
  • Michael Sabel - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Hans-Jakob Steiger - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Wei Zhang - Beijing Neurosurgical Institute, Peking, China
  • Daniel Hänggi - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland
  • Ulf Dietrich Kahlert - University Hospital Düsseldorf, Department of Neurosurgery, Düsseldorf, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocP063

doi: 10.3205/21dgnc351, urn:nbn:de:0183-21dgnc3513

Veröffentlicht: 4. Juni 2021

© 2021 Vargas-Toscano 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: Glioblastoma (GBM) is a lethal disease with limited clinical treatment options available. Recently, a new inhibitor targeting the prominent cancer signaling pathway mTOR was discovered (Rapalink-1), but its therapeutic potential on stem cell populations of GBM is unknown.

Methods: We applied a collection of physiological relevant organoid-like stem cell models of GBM and studied the effect of RL1 exposure on various cellular features as well as on the expression of mTOR signaling targets and stem cell molecules. We also undertook combination treatments with this agent and clinical GBM treatments tumor treating fields (TTFields) and the standard-of-care drug temozolomide, TMZ. Low nanomolar (nM) RL1 treatment significantly reduced cell growth, proliferation, migration, and clonogenic potential of our stem cell models. It acted synergistically to reduce cell growth when applied in combination with TMZ and TTFields. We performed an in silico analysis from the molecular data of diverse patient samples to probe for a relationship between the expression of mTOR genes, and mesenchymal markers in di erent GBM cohorts. We supported the in silico results with correlative protein data retrieved from tumor specimens.

Results: RL1 treatment significantly reduced cell growth, proliferation, migration and clonogenic potential of our stem cell models in the low nM range. It acted synergistically to reduce cell growth when applied in combination with TMZ and TTFields.

Conclusion: Our study further validates mTOR signaling as a druggable target in GBM and supports RL1, representing a promising therapeutic target in brain oncology.