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88th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

24.05. - 27.05.2017, Erfurt

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Combined Therapy of two RTKs: Erbitux und BGJ398 treatment in HNSCC cell lines

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  • corresponding author Christin Geißler - Hals-Nasen-Ohrenklinik des Universitätsklinikums Frankfurt, Frankfurt/M.
  • Jennis Gabrielpillai - Hals-Nasen-Ohrenklinik des Universitätsklinikums Frankfurt, Frankfurt/M.
  • Stefan Stein - Georg Speyer Haus, Frankfurt/M.
  • Marc Diensthuber - Hals-Nasen-Ohrenklinik des Universitätsklinikums Frankfurt, Frankfurt/M.
  • Jens Wagenblast - Praxis, Sinsheim
  • Timo Stöver - Hals-Nasen-Ohrenklinik des Universitätsklinikums Frankfurt, Frankfurt/M.

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 88. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Erfurt, 24.-27.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. Doc17hno142

doi: 10.3205/17hno142, urn:nbn:de:0183-17hno1424

Published: April 13, 2017

© 2017 Geißler et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Head and neck squamous cell carcinoma (HNSCC) derive from the mucosa of the aerodigestive area and still have worse prognoses. Despite of new treatment strategies like the epithelial growth factor receptor (EGFR) antibody Erbitux the survival rates have not increased yet. The native mucosa expresses several receptor tyrosine kinases (RTKs) like EGFR and fibroblast growth factor receptors (FGFRs) that regulate survival and proliferation. We hypnotized that the tumor cells can switch between the different RTKs to overcome the therapy. To improve therapy in HNSCC, this study determined the effectiveness of a combined treatment targeting EGFR and FGFR.

In an in-vitro drug trial Detroit-562, CAL-27 and PJ-15 cell lines were studied. BGJ398 (Novartis) that inhibits FGFRs and/or Erbitux (Merck) treatment was performed. Apoptosis was verified by caspases activity. The expression of the different RTKs was determined by immunocytochemistry and flow cytometry.

The cell lines expressed EGFR, KGFR and low amounts of FGFR1 and FGFR3. In all tested cell lines, the treatment with BGJ398 or Erbitux significantly reduce survival and proliferation. The combination of both drugs enhanced the effect at lower concentrations compared to the single drug treatment.

This study demonstrated that the combination of BGJ-398 and Erbitux is a promising treatment regime for HNSCCs. In the future, the reduction in drug concentrations may reduce side effects.

Supported by: Novartis Pharma GmbH

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