Characterization of a new small-molecule inhibitor of HDAC6 in glioblastoma

Histone deacetylase 6 (HDAC6) is an epigenetic modifier that is an attractive pharmacological target in cancer. In this work, we show that HDAC6 is elevated in glioblastoma, the most malignant and common brain tumor in adults, and in glioma stem cells. Moreover, we identified a new small-molecule inhibitor of HDAC6, called JOC1, which presents strong sensitivity for HDAC6 inhibition and exerts high cytotoxic activity, alone or in combination with temozolomide. Moreover, it is able to significantly reduce tumor growth in vivo. Transcriptomic analysis of patient derived glioma stem cells revealed an increase in cell differentiation and cell death as well as decrease in cell cycle activity and cell division as relevant cellular pathways whose activities are significantly altered by the treatment with JOC1. In conclusion, our data reveal the efficacy of a novel HDAC6 inhibitor in glioblastoma pre-clinical setting Glioblastoma cell line (GNS179)+/- small inhibitor JOC1 and pan-inihibitor SAHA