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The antiangiogenic compound axitinib demonstrates low toxicity and anti-tumoral effects against medulloblastoma

Pagnuzzi-Boncompagni, M.; Picco, V.; Vial, V.; Planas-Bielsa, V.; Vandenberghe, A.; Grepin, R.; Durivault, J.; Montemagno, C.; Martial, S.; Doyen, J.; Gavard, J.; Pages, G.

2020-09-19 cancer biology
10.1101/2020.09.18.301028 bioRxiv
Show abstract

Evolution of medulloblastoma (MB) treatments has increased the 5-year overall survival of to more than 70%. However, an increasing number of survivors face severe long-term adverse effects and associated morbidity due to multimodal treatments particularly harsh for the younger patients. Chemotherapeutic compounds inducing less adverse effects are key to improving the care of MB patients. The preclinical relevance of last generation anti-angiogenic compounds deserves to be fully assessed. Among these, axitinib showed the highest selectivity index for MB cells, efficiently reduced the growth rate of experimental tumors and led to less toxicity towards normal cells than did a reference treatment. In vivo, axitinib did not lead to acute toxicity in very young rats and was able to cross the blood brain barrier. Analysis of public databases shows that high expression of axitinib targets are of poor prognosis. Altogether, our results suggest that axitinib is a compelling candidate for MB treatment.

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