The Potential of Histone Deacetylase Inhibitors in Breast Cancer Therapy

Abstract

SUMMARY Breast cancer is the second leading cause of cancer-related mortality in women. Despite improvements in prevention, detection and treatment, breast cancer will be responsible for nearly 40,000 deaths in 2014. The function of histone deacetylases (HDACs) and their potential as therapeutic targets has become an area of intense investigation and small molecule inhibitors of HDACs (HDACi) are now being investigated as potential chemotherapeutics for breast cancer. In addition to altering chromatin structure through stabilization of histone acetylation, HDACi treatment induces the accumulation of acetylated isoforms of many nonhistone proteins, altering their structure and function. These structural changes influence protein–protein interactions and cellular processes including cell cycle arrest, apoptosis, autophagy, induction of reactive oxygen species and mitotic catastrophe. While the usefulness of these compounds as single agents for treatment of breast cancer is still under investigation, cotreatment with other therapies is being evaluated in a number of clinical trials.