Autoren:	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
Titel:	Safety and activity of the combination of ceritinib and dasatinib in osteosarcoma
Online-Publikationsdatum:	20-Okt-2020
Erscheinungsdatum:	2020
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5222
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Cancers 12 4
Seitenzahl oder Artikelnummer:	Art. 793
Verlag:	MDPI
Verlagsort:	Basel
Erscheinungsdatum:	2020
ISSN:	2072-6694
URL der Originalveröffentlichung:	https://doi.org/10.3390/cancers12040793
DOI der Originalveröffentlichung:	10.3390/cancers12040793
Enthalten in den Sammlungen:	JGU-Publikationen