<br>AKR1C3 在癌症中的作用：从多方面的作用到治疗策略,Frontiers in Pharmacology

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AKR1C3 在癌症中的作用：从多方面的作用到治疗策略
Frontiers in Pharmacology ( IF 4.4 ) Pub Date : 2024-03-08 , DOI: 10.3389/fphar.2024.1378292
Mengnan Li ₁ , Limin Zhang _{2,

3} , Jiahui Yu ₁ , Xiaoxiao Wang ₁ , Le Cheng ₁ , Zhaowu Ma ₁ , Xiaoguang Chen ₁ , Lingzhi Wang _{4,

5,

6,

7} , Boon Cher Goh _{4,

5,

6,

7,

8}

Affiliation

醛酮还原酶家族 1 成员 C3 (AKR1C3)，也称为 5 型 17β-羟基类固醇脱氢酶 (17β-HSD5) 或前列腺素 F (PGF) 合酶，在雄激素生物合成中充当关键酶。它催化弱雄激素、雌酮（一种弱雌激素）和 PGD2 分别转化为强雄激素（睾酮和 5α-二氢睾酮）、17β-雌二醇（一种强雌激素）和 11β-PGF2α。 AKR1C3 水平升高会激活雄激素受体 (AR) 信号通路，导致肿瘤复发并产生对癌症治疗的耐药性。 AKR1C3 的过度表达是一种致癌因子，促进癌细胞增殖、侵袭和转移，与癌症患者的不良预后和总生存期相关。抑制 AKR1C3 已被证明在抑制肿瘤进展和克服治疗耐药方面具有强大的功效。因此，AKR1C3抑制剂的开发和设计引起了研究人员越来越多的兴趣，近年来取得了重大进展。新型 AKR1C3 抑制剂，包括天然产物和基于其结构和框架设计的现有药物的类似物，在世界各地的实验室中不断被发现和开发。 AKR1C3 酶已成为癌症进展和治疗耐药的关键因素，给癌症治疗带来了挑战。本综述旨在全面分析 AKR1C3 在癌症发展中的作用、其对治疗耐药的影响以及用于肿瘤治疗的 AKR1C3 抑制剂开发的最新进展。

"点击查看英文标题和摘要"

AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies

Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17β-estradiol (a potent estrogen), and 11β-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Novel AKR1C3 inhibitors, including natural products and analogues of existing drugs designed based on their structures and frameworks, continue to be discovered and developed in laboratories worldwide. The AKR1C3 enzyme has emerged as a key player in carcinoma progression and therapeutic resistance, posing challenges in cancer treatment. This review aims to provide a comprehensive analysis of AKR1C3’s role in carcinoma development, its implications in therapeutic resistance, and recent advancements in the development of AKR1C3 inhibitors for tumor therapies.

更新日期：2024-03-08

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