EP4405680A1 — Methods for improving the efficacy of hdac inhibitor therapy and predicting the response to treatment with hdac inhibitor

USPTO Abstract

Investigating the impact of Tau protein expression in cancer cell lines, Inventors have demonstrated that the Tau expression is associated with an increased resistance to HDAC inhibittors. Briefly in the present invention, inventors report that Tau expression in breast cancer cell lines causes resistance to the anti-cancer effects of histone deacetylase inhibitors, by preventing histone deacetylase inhibitor-inducible gene expression and remodeling of chromatin structure. Inventors identify Tau as a protein recognizing and binding to core histone when H3 and H4 are devoid of any post-translational modifications or acetylated H4 that increases the Tau's affinity. In addition, they demonstrate that the interaction between Tau and histones prevents further histone H3 post-translational modifications induced by histone deacetylase-inhibitor treatment by maintaining a more compact chromatin structure The present invention relates to means to improve the bioavailability of histone deacetylase (HDAC) inhibitor and thereby also improve the efficacy of histone deacetylase (HDAC) inhibitor treatments.