Histone deacetylases: A novel class of therapeutic targets for pancreatic cancer

Pancreatic cancer is the seventh leading cause of cancer death worldwide, with a low 5-year survival rate. Novel agents are urgently necessary to treat the main pathological type, known as pancreatic ductal carcinoma (PDAC). The dysregulation of histone deacetylases (HDACs) has been identified in association with PDAC, which can be more easily targeted by small molecular inhibitors than gene mutations and may represent a therapeutic breakthrough for PDAC. However, the contributions of HDACs to PDAC remain controversial, and pharmacokinetic challenges have limited the application of HDAC inhibitors (HDACis) in PDAC. This review summarizes the mechanisms associated with success and failure of HDACis in PDAC and discusses the recent progress made in HDACi development and application, such as combination therapies designed to enhance efficacy. More precise strategies involving HDACis might eventually improve the outcomes of PDAC treatment.