人类 ALDH 包含 19 个亚家族，其中 ALDH1A1、ALDH1A3、ALDH3A1、ALDH5A1、ALDH7A1 和 ALDH18A1 与 CSC 相关。研究表明，ALDH 也可能与耐药性有关，标准化疗方案对疾病复发阶段的患者无效。现有的化疗药物可以消除大部分肿瘤，但通常对表达 ALDH 群体的 CSC 无效。今后，针对 ALDH 的治疗对于治疗患者的复发后来说是令人信服的。互连信号机制的联合疗法似乎有望提高总体无病生存率。因此，通过 ALDH 抑制剂和免疫疗法来靶向 ALDH 可能会为转化研究创造一个新的平台。本综述旨在填补 ALDH1 家族成员之间在细胞信号传导机制方面的空白，强调它们作为分子靶点使复发性肿瘤敏感的潜力，并针对当前的进展和缺陷提出未来的发展。这篇综述总结了癌症干细胞的作用及其通过维持肿瘤微环境而上调的作用，其中特别强调了 ALDH。它讨论了 ALDH 家族蛋白的调节以及 ALDH 和 CSC 之间与癌症代谢相关的串扰。此外，它还建立了 ALDH 信号传导机制与其特定靶向抑制剂之间的相关性，以及它们在各种癌症中的功能模块性、生物利用度和机制作用。版权所有 © 2024。由 Elsevier Inc. 出版。

Human ALDH comprise 19 subfamilies in which ALDH1A1, ALDH1A3, ALDH3A1, ALDH5A1, ALDH7A1, and ALDH18A1 are implicated in CSC. Studies have shown that ALDH can also be involved in drug resistance and standard chemotherapy regimens are ineffective in treating patients at the stage of disease recurrence. Existing chemotherapeutic drugs eliminate the bulk of tumors but are usually not effective against CSC which express ALDH+ population. Henceforth, targeting ALDH is convincing to treat the patient's post-relapse. Combination therapies that interlink signaling mechanisms seem promising to increase the overall disease-free survival rate. Therefore, targeting ALDH through ALDH inhibitors along with immunotherapies may create a novel platform for translational research. This review aims to fill in the gap between ALDH1 family members in relation to its cell signaling mechanisms, highlighting their potential as molecular targets to sensitize recurrent tumors and bring forward the future development concerning the current progress and draw backs. This review summarizes the role of cancer stem cells and their upregulation by maintaining the tumor microenvironment in which ALDH is specifically highlighted. It discusses the regulation of ALDH family proteins and the crosstalk between ALDH and CSC in relation to cancer metabolism. Furthermore, it establishes the correlation between ALDH involved signaling mechanisms and their specific targeted inhibitors, as well as their functional modularity, bioavailability, and mechanistic role in various cancers.Copyright © 2024. Published by Elsevier Inc.