Mechanisms and importance of histone modification enzymes in targeted therapy for hepatobiliary cancers

Hepatobiliary cancers have poor prognosis due to their high level of invasiveness, distant metastasis, and chemotherapy resistance. Hepatocellular carcinoma is the most common type of hepatobiliary cancers representing the fourth leading cause of cancer death worldwide. There is an urgent need to identify the molecular drivers of hepatobiliary cancers to improve the therapeutic outcomes and patient prognosis. Histone modification is an important biological process that is critical in the regulation of epigenetic maintenance and modifications which in turn exert critical impacts on gene expression and chromatin structure stability. Histones may undergo a series of enzyme-catalyzed post-translational modifications such as acetylation, methylation, phosphorylation, ubiquitination, SUMOylating, crotonylation, and 2-hydroxyisobutyrylation. Dysregulation of histone-modifying enzyme may cause multiple diseases including cancers. As such, histone-modifying enzymes constitute a group of potential therapeutic targets. The aim of this review is to summarize the current understanding of the role of histone modification enzymes in regulating epigenetic alterations, cancer development, and their potential as therapeutic targets for hepatobiliary cancers.