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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1378292/full |
| _version_ | 1827323229095591936 |
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| author | Mengnan Li Limin Zhang Limin Zhang Jiahui Yu Xiaoxiao Wang Le Cheng Zhaowu Ma Xiaoguang Chen Lingzhi Wang Lingzhi Wang Lingzhi Wang Lingzhi Wang Boon Cher Goh Boon Cher Goh Boon Cher Goh Boon Cher Goh Boon Cher Goh |
| author_facet | Mengnan Li Limin Zhang Limin Zhang Jiahui Yu Xiaoxiao Wang Le Cheng Zhaowu Ma Xiaoguang Chen Lingzhi Wang Lingzhi Wang Lingzhi Wang Lingzhi Wang Boon Cher Goh Boon Cher Goh Boon Cher Goh Boon Cher Goh Boon Cher Goh |
| author_sort | Mengnan Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-25T01:41:52Z |
| format | Article |
| id | doaj.art-2f0a43eeeb20456f86e43c364fce31d1 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-25T01:41:52Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-2f0a43eeeb20456f86e43c364fce31d12024-03-08T04:40:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.13782921378292AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategiesMengnan Li0Limin Zhang1Limin Zhang2Jiahui Yu3Xiaoxiao Wang4Le Cheng5Zhaowu Ma6Xiaoguang Chen7Lingzhi Wang8Lingzhi Wang9Lingzhi Wang10Lingzhi Wang11Boon Cher Goh12Boon Cher Goh13Boon Cher Goh14Boon Cher Goh15Boon Cher Goh16School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, ChinaJingzhou Hospital of Traditional Chinese Medicine, Jingzhou, ChinaThe Third Clinical Medical College of Yangtze University, Jingzhou, ChinaSchool of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, ChinaSchool of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, ChinaSchool of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, ChinaSchool of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, ChinaSchool of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, ChinaDepartment of Haematology–Oncology, National University Cancer Institute, Singapore, SingaporeNUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCancer Science Institute of Singapore, National University of Singapore, Singapore, SingaporeDepartment of Haematology–Oncology, National University Cancer Institute, Singapore, SingaporeNUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCancer Science Institute of Singapore, National University of Singapore, Singapore, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeAldo-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.https://www.frontiersin.org/articles/10.3389/fphar.2024.1378292/fullAKR1C3carcinoma progressiontherapeutic resistanceinhibitorscombination therapies |
| spellingShingle | Mengnan Li Limin Zhang Limin Zhang Jiahui Yu Xiaoxiao Wang Le Cheng Zhaowu Ma Xiaoguang Chen Lingzhi Wang Lingzhi Wang Lingzhi Wang Lingzhi Wang Boon Cher Goh Boon Cher Goh Boon Cher Goh Boon Cher Goh Boon Cher Goh AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies Frontiers in Pharmacology AKR1C3 carcinoma progression therapeutic resistance inhibitors combination therapies |
| title | AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies |
| title_full | AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies |
| title_fullStr | AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies |
| title_full_unstemmed | AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies |
| title_short | AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies |
| title_sort | akr1c3 in carcinomas from multifaceted roles to therapeutic strategies |
| topic | AKR1C3 carcinoma progression therapeutic resistance inhibitors combination therapies |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1378292/full |
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