Small molecule HDAC inhibitors: Promising agents for breast cancer treatment

Bioorg Chem. 2019 Oct:91:103184. doi: 10.1016/j.bioorg.2019.103184. Epub 2019 Aug 5.

Abstract

Breast cancer, a heterogeneous disease, is the most frequently diagnosed cancer and the second leading cause of cancer-related death among women worldwide. Recently, epigenetic abnormalities have emerged as an important hallmark of cancer development and progression. Given that histone deacetylases (HDACs) are crucial to chromatin remodeling and epigenetics, their inhibitors have become promising potential anticancer drugs for research. Here we reviewed the mechanism and classification of histone deacetylases (HDACs), association between HDACs and breast cancer, classification and structure-activity relationship (SAR) of HDACIs, pharmacokinetic and toxicological properties of the HDACIs, and registered clinical studies for breast cancer treatment. In conclusion, HDACIs have shown desirable effects on breast cancer, especially when they are used in combination with other anticancer agents. In the coming future, more multicenter and randomized Phase III studies are expected to be conducted pushing promising new therapies closer to the market. In addition, the design and synthesis of novel HDACIs are also needed.

Keywords: Anticancer drug; Breast cancer; Clinical trials; HDAC inhibitors; HDACs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology
  • Female
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / chemistry*
  • Humans
  • Models, Molecular*
  • Molecular Docking Simulation
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*

Substances

  • Histone Deacetylase Inhibitors
  • Small Molecule Libraries
  • Histone Deacetylases