Selective Inhibitors of Zinc-Dependent Histone Deacetylases. Therapeutic Targets Relevant to Cancer

Histone deacetylases (HDACs), which act on acetylated histones and/or other non-histone protein substrates, represent validated epigenetic targets for the treatment of cancer and other human diseases. The inhibition of HDAC activity was shown to induce cell cycle arrest, differentiation, apoptosis as well as a decrease in proliferation, angiogenesis, migration, and cell resistance to chemotherapy. Targeting single HDAC isoforms with selective inhibitors will help to reveal the role of individual HDACs in cancer development or uncover further biological consequences of protein acetylation. This review focuses on conventional zinc-containing HDACs. In its first part, the biological role of individual HDACs in various types of cancer is summarized. In the second part, promising HDAC inhibitors showing activity both in enzymatic and cell-based assays are surveyed with an emphasis on the inhibitors selective to the individual HDACs.