Antiangiogenic Compound Axitinib Demonstrates Low Toxicity and Antitumoral Effects against Medulloblastoma.

Autor: Pagnuzzi-Boncompagni M; Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco., Picco V; Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco., Vial V; Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco., Planas-Bielsa V; Polar Biology Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco., Vandenberghe A; Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco., Daubon T; Institut de Biochimie et Génétique Cellulaires (IBGC), CNRS, University of Bordeaux, UMR 5095, 33000 Bordeaux, France., Derieppe MA; Animalerie Mutualisée, Service Commun des Animaleries, University of Bordeaux, 33600 Pessac, France., Montemagno C; Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco., Durivault J; Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco., Grépin R; Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco., Martial S; Centre Antoine Lacassagne, Institute for Research on Cancer and Aging of Nice (IRCAN), University Nice Cote d'Azur, CNRS UMR 7284, INSERM U1081, 06189 Nice, France., Doyen J; Department of Radiation Oncology, Centre Antoine-Lacassagne, University of Côte d'Azur, Fédération Claude Lalanne, 06189 Nice, France., Gavard J; Team SOAP, CRCINA, INSERM, CNRS, Université de Nantes, 44000 Nantes, France.; Integrated Center of Oncology, 44800 St. Herblain, France., Pagès G; Biomedical Department, Centre Scientifique de Monaco, 98000 Monaco, Monaco.; Centre Antoine Lacassagne, Institute for Research on Cancer and Aging of Nice (IRCAN), University Nice Cote d'Azur, CNRS UMR 7284, INSERM U1081, 06189 Nice, France.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Dec 24; Vol. 14 (1). Date of Electronic Publication: 2021 Dec 24.
DOI: 10.3390/cancers14010070
Abstrakt: Background: Despite the improvement of medulloblastoma (MB) treatments, survivors face severe long-term adverse effects and associated morbidity following multimodal treatments. Moreover, relapses are fatal within a few months. Therefore, chemotherapies inducing fewer adverse effects and/or improving survival at relapse are key for MB patients. Our purpose was to evaluate the last-generation antiangiogenic drugs for their relevance in the therapeutic arsenal of MB.
Methods: We screened three EMA- and FDA-approved antiangiogenic compounds (axitinib, cabozantinib and sunitinib) for their ability to reduce cell viability of five MB cell lines and their low toxicity towards two normal cell lines in vitro. Based on this screening, single-agent and combination therapies were designed for in vivo validation.
Results: Axitinib, cabozantinib and sunitinib decreased viability of all the tested tumor cells. Although sunitinib was the most efficient in tumor cells, it also impacted normal cells. Therefore, axitinib showed the highest selectivity index for MB cells as compared to normal cells. The compound did not lead to acute toxicity in juvenile rats and crossed the blood-brain barrier. Moreover, axitinib efficiently reduced the growth rate of experimental brain tumors. Analysis of public databases showed that high expression of axitinib targets correlates with poor prognosis.
Conclusion: Our results suggest that axitinib is a compelling candidate for MB treatment.
Databáze: MEDLINE
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