Xiang Xue-Song, Li Peng-Cheng, Wang Wen-Quan, Liu Liang
Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Biochim Biophys Acta Rev Cancer. 2022 Jan;1877(1):188676. doi: 10.1016/j.bbcan.2022.188676. Epub 2022 Jan 10.
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.
胰腺癌是全球癌症死亡的第七大主要原因，5年生存率较低。迫切需要新型药物来治疗主要病理类型，即胰腺导管癌（PDAC）。已发现组蛋白脱乙酰酶（HDACs）失调与PDAC相关，与基因突变相比，小分子抑制剂更容易靶向HDACs，这可能代表着PDAC治疗的一个突破。然而，HDACs对PDAC的作用仍存在争议，药代动力学方面的挑战限制了HDAC抑制剂（HDACis）在PDAC中的应用。本综述总结了HDACis在PDAC中成功与失败相关的机制，并讨论了HDACi开发和应用方面的最新进展，如旨在提高疗效的联合疗法。涉及HDACis的更精确策略最终可能改善PDAC的治疗效果。
