Selective inhibition of Histone Deacetylase 8 as a novel therapeutic strategy for the treatment of high-risk neuroblastoma

Aims: Expression studies of primary neuroblastoma samples from the German Neuroblastoma Trial revealed histone deacetylase 8 (HDAC8) to be upregulated in stage 4 patients, associated with a significantly worse prognosis. Here, we investigated the anti-neuroblastoma activity of HDAC8-selective inhibitors (HDAC8i) in vitro and in vivo. Methods: Treatment of neuroblastoma cell lines and mouse xenografts were used to evaluate the therapeutic potential of HDAC8i. Selectivity for HDAC8 was verified by absence of off-target acetylation in Western Blot at the relevant in vitro and in vivo administration of HDAC8i. In vi…