The emergence of specific HDAC inhibitors and their clinical efficacy in the treatment of hematologic malignancies and breast cancer

Abstract

Epigenetic modification of gene expression through inhibition of histone deacetylases (HDAC) represents a promising potential clinical strategy for a variety of conditions, including cancer, autoimmunity and transplantation, polyglutamine disorders, neurological diseases, and heart disease. 1–4 Numerous histone deacetylase inhibitors (HDI) have been developed, showing varying degrees of specificity across classes or isotypes of HDACs. Early experience demonstrated the efficacy of less specific, “pan/global” HDIs (e.g. vorinostat, panbinostat, and abexinostat) in the treatment of specific hematological malignancies, but was tempered by significant toxicity exhibited by the inhibitor class. As the preclinical and clinical evaluation of this strategy has progressed, the field has shifted toward a focus on the development and investigation of more specific HDIs;5 hoping to limit toxicity and unintended non-target effects of HDI. Herein, we seek to review the trend in clinical research toward the development of class and isoformspecific HDIs, highlighting their clinical efficacies and limitations in the treatment of hematologic and breast cancers in order to underscore their potential to allow for the improvement of clinical outcomes with less toxicity and unintended non-target effects.