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DKFZ Junior Group Brain Tumor Translational Targets

Dr. Violaine Goidts

Targeting GSCs to achieve complete degeneration of glioblastoma; a) Currently, the resistance of GSCs to radio- and chemotherapy allows this rare subpopulation of cells to persist after GBM treatment. Patients relapse with an aggressive tumour enriched in GSCs. b) Targeting GSCs with additional therapeutics will deplete this resistant sub-population, allowing complete degeneration of the tumour.
© dkfz.de

Due to its location, aggressiveness and diffuse growth pattern, glioblastoma therapy is tremendously challenging and advances in the field are urgently needed. Much evidence has been gathered to reveal a small sub-population of cancer cells, known as glioblastoma stem-like cells (GSCs), which are thought to be responsible for the current therapy resistance of glioblastoma. In this respect, considerable effort must be directed towards the targeting of GSCs.
Recently, the advent of high-throughput next-generation sequencing technologies has led to a new era in the study of de novo mutations, helping to uncover disease precondition and mechanism. However, these informative analyses do not account for post-translational modifications. High-throughput phenotypic screens, which form the basis of the strategy of our group, have proven to resolve this issue and offer a large panel of candidate genes or small-molecule inhibitors.
This great resource provided by these functional screens supports our ambition to further discover new druggable therapeutic targets or new compounds to treat glioblastoma. We aim to verify their efficacy in pre-clinical studies and to test them in clinical trials.

Contact

Dr. Violaine Goidts
Brain Tumor Translational Targets (B067)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 580
69120 Heidelberg
Tel: +49 6221 42-4635

Selected Publications

  • A novel patient stratification strategy to enhance the therapeutic efficacy of dasatinib in glioblastoma. Alhalabi OT, Fletcher MNC, Hielscher T, Kessler T, Lokumcu T, Baumgartner U, Wittmann E, Schlue S, Göttmann M, Rahman S, Hai L, Hansen-Palmus L, Puccio L, Nakano I, Herold-Mende C, Day BW, Wick W, Sahm F, Phillips E, Goidts V.Neuro Oncol. 2022 Jan 5;24(1):39-51. doi: 10.1093/neuonc/noab158.
  • PFKFB4 interacts with FBXO28 to promote HIF-1? signaling in glioblastoma. Phillips E, Balss J, Bethke F, Pusch S, Christen S, Hielscher T, Schnölzer M, Fletcher MNC, Habel A, Tessmer C, Brenner LM, Göttmann M, Capper D, Herold-Mende C, von Deimling A, Fendt SM, Goidts V.Oncogenesis. 2022 Sep 17;11(1):57. doi: 10.1038/s41389-022-00433-3.
  • PERK-mediated expression of peptidylglycine ?-amidating monooxygenase supports angiogenesis in glioblastoma. Soni H, Bode J, Nguyen CDL, Puccio L, Neßling M, Piro RM, Bub J, Phillips E, Ahrends R, Eipper BA, Tews B, Goidts V.Oncogenesis. 2020 Feb 13;9(2):18. doi: 10.1038/s41389-020-0201-8.
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