聚ADP核糖水解酶在胆管癌诊治中的研究进展

摘要/Abstract

摘要： 胆管癌(CCA)是一类具有高度侵袭性且治疗手段有限的恶性肿瘤,现有化疗、靶向治疗及免疫治疗均面临耐药性增加和获益人群有限的瓶颈。聚ADP核糖水解酶(PARG)是维持聚 ADP 核糖基化稳态的关键水解酶,在CCA组织中呈高表达,且与肿瘤进展及预后不良密切相关。本文系统综述了PARG在CCA诊治中的作用机制:其通过调控DNA损伤修复和复制应激维持肿瘤细胞存活,通过Hippo/YAP/TAZ信号通路驱动化疗耐药并促进基质重塑,并通过STAT3及cGAS-STING通路调控免疫微环境。本文重点阐述了PARG在CCA诊断、预后评估与治疗中的应用进展:作为诊断和预后标志物的潜在临床价值,PARG抑制剂单药及联合吉西他滨/顺铂、免疫检查点抑制剂的前临床疗效,以及基于PARG表达、单链DNA缺口和免疫特征的多维精准分层策略。同时,本文分析了PARG靶向治疗面临的疗效异质性、转化成本、伦理问题及可及性等挑战,并提出了从回顾性标志物验证到前瞻性联合治疗临床试验的转化思路,以期为CCA的精准诊疗提供新思路。

关键词: 胆管癌, 聚ADP核糖水解酶, PARG抑制剂, 联合治疗

宁雨湘, 黄罡. 聚ADP核糖水解酶在胆管癌诊治中的研究进展[J]. 肝脏, 2026, 31(8): 1073-1078.

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