Histone Deacetylase 10-inhibitor Co-Treatment in Cancer

Histone deacetylase inhibitors (HDACi) are promising anticancer agents and are currently being evaluated in clinical trials. However, due to their unselective action, pan-HDACi exhibit dose-limiting side-effects restricting their full potential in anti-cancer therapy. Therefore, characterization of the molecular function of single HDAC isozymes is of major importance for a targeted therapy with less side-effects. We show that HDAC10 overexpression mediated cell survival and targeting of HDAC10 sensitized tumor cells for cytotoxic drug treatment and it correlates with progression or recurrence of neuroblastoma in vivo. These results demonstrate for the first time that HDAC10 induces an alternative lysosomal-mediated tumor cell death pathway, re-sensitizes cells for cytotoxic drugs and may thus be a novel strategy for neuroblastoma therapy.

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