title: Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy.
abstract: Aldo-keto reductases comprise of AKR1C1-AKR1C4, four enzymes that catalyze NADPH dependent reductions and have been implicated in biosynthesis, intermediary metabolism, and detoxification. Recent studies have provided evidences of strong correlation between the expression levels of these family members and the malignant transformation as well as the resistance to cancer therapy. Mechanistically, most studies focus on the catalytic-dependent function of AKR1C isoforms, like their impeccable roles in prostate cancer, breast cancer, and drug resistance due to the broad substrates specificity. However, accumulating clues showed that catalytic-independent functions also played critical roles in regulating biological events. This review summarizes the catalytic-dependent and -independent roles of AKR1Cs, as well as the small molecule inhibitors targeting these family members.
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Zeng
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Chang
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
authors.forename: Mei-Dan
authors.initials: MD
authors.lastname: Ying
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Cao
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
authors.forename: Qiao-Jun
authors.initials: QJ
authors.lastname: He
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University Hangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
keywords: aldo–keto reductases; catalytic-dependent; catalytic-independent; inhibitor; therapy