Tackling triple negative breast cancer with HDAC inhibitors: 6 is the isoform!

Abstract

Triple negative breast cancer (TNBC) is a highly aggressive breast cancer subtype characterized by the lack in the expression of estrogen and progesterone receptors, and human epidermal growth factor receptors 2. TNBC stands out among other breast cancers subtypes for its high aggressiveness and invasiveness, and for the limited therapeutic options available, which justify the poor survival rates registered for this breast cancer subtype. Compelling new evidence pointed out the role of epigenetic modifications in cancer, prompting tumor cell uncontrolled proliferation, epithelial-to-mesenchymal transition, and metastatic events. In this review we showcase the latest evidence supporting the involvement of histone deacetylase 6 (HDAC6) in cancer pathways strictly related to TNBC subtype, also tracking the latest advancements in the identification of novel HDAC6 inhibitors which showed efficacy in TNBC models, offering insights into the potential of targeting this key epigenetic player as an innovative therapeutic option for the treatment of TNBC.

Keywords: Apoptosis; Chemoresistance; Epigenetics; HDAC6 inhibitors; Triple negative breast cancer.