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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
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
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Cancers
Pages or article number: Art. 793
Publisher: MDPI
Publisher place: Basel
Issue date: 2020
ISSN: 2072-6694
Publisher URL:
Publisher DOI: 10.3390/cancers12040793
Appears in collections:JGU-Publikationen

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