靶向醛脱氢酶在肝细胞癌发生机制与治疗策略中的研究进展

Targeting aldehyde dehydrogenase in hepatocellular carcinoma: mechanistic insights and therapeutic advances

摘要:

肝细胞癌（HCC）是一种高度异质性、预后差的恶性肿瘤，其发生发展与氧化应激、代谢重编程及肿瘤微环境密切相关。醛脱氢酶（ALDH）在HCC中不仅参与氧化应激调控、糖脂代谢改变和肿瘤干细胞维持，还在免疫逃逸中发挥重要作用，成为潜在的治疗靶点。本文系统综述了ALDH在HCC中的表达特征与功能机制，重点评述了ALDH抑制剂（如双硫仑、二乙氨基苯甲醛）及基于ALDH的肽疫苗等治疗策略的研究进展，并探讨其在联合免疫治疗和化疗中的应用前景。现有证据表明，靶向ALDH有望抑制肿瘤生长、逆转耐药并增强抗肿瘤免疫反应。未来应聚焦于优化药物选择性与安全性，并探索个体化联合治疗方案，以改善HCC患者的预后。

Abstract:

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with poor prognosis, closely linked to oxidative stress, metabolic reprogramming, and tumor microenvironment alterations. Aldehyde dehydrogenase (ALDH) plays multifaceted roles in HCC by regulating oxidative stress, modulating glucose and lipid metabolism, sustaining cancer stem cell properties, and promoting immune evasion, making it a promising therapeutic target. This review summarizes the expression patterns and mechanistic functions of ALDH in HCC, highlights advances in ALDH-targeted therapies, including inhibitors such as disulfiram and diethylaminobenzaldehyde, and ALDH-based peptide vaccines-and discusses their potential in combination with immunotherapy and chemotherapy. Current evidence suggests that ALDH inhibition can suppress tumor growth, reverse drug resistance, and enhance antitumor immunity. Future research should aim to improve drug selectivity and safety, and to develop personalized combination strategies to optimize clinical outcomes in HCC patients.