Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-5222
Authors: | Beck, Olaf Paret, Claudia Russo, Alexandra Burhenne, Jürgen Fresnais, Margaux Steimel, Kevin Seidmann, Larissa Wagner, Daniel-Christoph Vewinger, Nadine Lehmann, Nadine Sprang, Maximilian Backes, Nora Roth, Lea Neu, Marie Astrid Wingerter, Arthur Henninger, Nicole EL Malki, Khalifa Otto, Henrike Alt, Francesca Desuki, Alexander Kindler, Thomas Faber, Jörg |
Title: | Safety and activity of the combination of ceritinib and dasatinib in osteosarcoma |
Online publication date: | 20-Oct-2020 |
Year of first publication: | 2020 |
Language: | english |
Abstract: | Abstract: Osteosarcoma (OS) is the second most common cause of cancer-related death in pediatric patients. The insulin-like growth factor (IGF) pathway plays a relevant role in the biology of OS but no IGF targeted therapies have been successful as monotherapy so far. Here, we tested the e ect of three IGF specific inhibitors and tested ceritinib as an o -target inhibitor, alone or in combination with dasatinib, on the proliferation of seven primary OS cells. Picropodophyllin, particularly in combination with dasatinib and the combination ceritinib/dasatinib were e ective in abrogating the proliferation. The ceritinib/dasatinib combination was applied to the primary cells of a 16-year-old girl with a long history of lung metastases, and was more e ective than cabozantinib and olaparib. Therefore, the combination was used to treat the patient. The treatment was well tolerated, with toxicity limited to skin rush and diarrhea. A histopathological evaluation of the tumor after three months of therapy indicated regions of high necrosis and extensive infiltration of macrophages. The extension of the necrosis was proportional to the concentration of dasatinib and ceritinib in the area, as analysed by an ultra performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS). After the cessation of the therapy, radiological analysis indicated a massive growth of the patient’s liver metastases. In conclusion, these data indicate that the combination of ceritinib/dasatinib is safe and may be used to develop new therapy protocols. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-5222 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Cancers 12 4 |
Pages or article number: | Art. 793 |
Publisher: | MDPI |
Publisher place: | Basel |
Issue date: | 2020 |
ISSN: | 2072-6694 |
Publisher URL: | https://doi.org/10.3390/cancers12040793 |
Publisher DOI: | 10.3390/cancers12040793 |
Appears in collections: | JGU-Publikationen |
Files in This Item:
File | Description | Size | Format | ||
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faber_joerg-safety_and_act-20201016144537055.pdf | 2.33 MB | Adobe PDF | View/Open |