Currently,much attention has been paid to the use of the isotype HDAC8 as a drug target. HDAC8 is a zinc-dependent class I HDAC containing 377 amino acids (aa, 42 kDa). The forced overexpression of HDAC1, 6, or 8 or their knockdown by specific short interfering RNAs (siRNAs) revealed the involvement of these HDACs in cancer cell invasion and matrix metallopeptidase 9 (MMP-9) expression in MCF-7 and MDA-MB-231 breast cancer cells. Among 20 breast cancer patients, 17 (85%) showed positive immunoreactivity for HDAC8. Currently, major efforts are focused on developing specific and selective HDAC isoform inhibitors and investigating combination therapies, with the aim of increasing potency against specific cancer types and overcoming drug resistance. Studies have also evaluated the therapeutic effect of the HDAC8-specific inhibitor PCI-34051 on malignant peripheral nerve sheath tumors and T-cell lymphomas. Developing potent selective inhibitors that specifically target HDAC8 with fewer adverse effects comparedwith those of pan-HDAC inhibitors is a current challenge.
Hsieh C L, et al. Alterations in histone deacetylase 8 lead to cell migration and poor prognosis in breast cancer[J]. Life sciences, 2016, 151: 7-14.