Will broad-spectrum histone deacetylase inhibitors be superseded by more specific compounds?

Abstract

Histone deacetylase (HDAC) inhibitors can induce differentiation, cell cycle and growth arrest or in certain cases apoptosis in cancer cells. In a remarkably short period of time, especially considering that their mechanism of action remains largely undefined, HDAC inhibitors have realized both success and failure as therapeutics for cancer in clinical trials. Notably, the pleiotropic HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and depsipeptide, have shown efficacy in a wide range of cancers, in particular for cutaneous T-cell lymphoma (CTCL), and are progressing in phase II clinical studies. However, evidence is accumulating that specific HDAC enzymes are important with respect ..