文章：

醛脱氢酶1A3（ALDH1A3）研究新视野：针对胶质母细胞瘤、间皮瘤及其他癌症中ALDH1A3依赖性通路的新型特异性抑制剂与活性探针

A New Vista of Aldehyde Dehydrogenase 1A3 (ALDH1A3): New Specific Inhibitors and Activity-Based Probes Targeting ALDH1A3 Dependent Pathways in Glioblastoma, Mesothelioma and Other Cancers

原文发布日期：28 June 2024

DOI: 10.3390/cancers16132397

类型: Article

开放获取: 是

英文摘要：

Aldehyde dehydrogenases of the subfamily 1A (ALDH1A) are enzymes necessary for the oxidation of all-transor 9-cisretinal to retinoic acid (RA). Retinoic acid and its derivatives are important for normal development and maintenance of epithelia, reproduction, memory, and immune function in adults. Moreover, in recent years, it has been demonstrated that ALDH1A members are also expressed and functional in several human cancers where their role is not limited to the synthesis of RA. Here, we review the current knowledge about ALDH1A3, one of the 1A isoforms, in cancers with an emphasis on two of the deadliest tumors that affect humans: glioblastoma multiforme and mesothelioma. In both tumors, ALDH1A3 is considered a negative prognostic factor, and its level correlates with excessive proliferation, chemoresistance, and invasiveness. We also review the recent attempts to develop both ALDH1A3-selective inhibitors for cancer therapy and ALDH1A3-specific fluorescent substrates for fluorescence-guided tumor resection.

摘要翻译： 

亚家族1A醛脱氢酶（ALDH1A）是将全反式或9-顺式视黄醛氧化为视黄酸（RA）的关键酶类。视黄酸及其衍生物对成人上皮组织的正常发育与维持、生殖功能、记忆能力及免疫功能具有重要作用。近年来研究表明，ALDH1A家族成员在多种人类癌症中同样具有表达及功能活性，其作用不仅限于RA的合成。本文聚焦于1A亚型中的ALDH1A3，系统综述其在恶性肿瘤中的研究进展，重点探讨其对人类最具致命性的两种肿瘤——多形性胶质母细胞瘤和间皮瘤的作用机制。在这两种肿瘤中，ALDH1A3均被视为不良预后因子，其表达水平与肿瘤过度增殖、化疗耐药及侵袭转移特性密切相关。同时，本文还评述了当前针对癌症治疗研发ALDH1A3选择性抑制剂的最新进展，以及用于荧光引导肿瘤切除术的ALDH1A3特异性荧光底物的开发策略。

原文链接：

A New Vista of Aldehyde Dehydrogenase 1A3 (ALDH1A3): New Specific Inhibitors and Activity-Based Probes Targeting ALDH1A3 Dependent Pathways in Glioblastoma, Mesothelioma and Other Cancers