Aldo-keto reductases and cancer drug resistance

Penning, Trevor M. (author), Jonnalagadda, Sravan (author), Trippier, Paul C. (author), Lanišnik-Rižner, Tea (author)

Human aldo-keto reductases (AKRs) catalyze the NADPH-dependent reduction of carbonyl groups to alcohols for conjugation reactions to proceed. They are implicated in resistance to cancer chemotherapeutic agents either because they are directly involved in their metabolism or help eradicate the cellular stress created by these agents (e.g., reactive oxygen species and lipid peroxides). Furthermore, this cellular stress activates the Nuclear factor-erythroid 2 p45-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 pathway. As many human AKR genes are upregulated by the NRF2 transcription factor, this leads to a feed-forward mechanism to enhance drug resistance. Resistance to major classes of chemotherapeutic agents (anthracyclines, mitomycin, cis-platin, antitubulin agents, vinca alkaloids, and cyclophosphamide) occurs by this mechanism. Human AKRs also catalyze the synthesis of androgens and estrogens and the elimination of progestogens and are involved in hormonal-dependent malignancies. They are upregulated by antihormonal therapy providing a second mechanism for cancer drug resistance. Inhibitors of the NRF2 system or pan-AKR1C inhibitors offer promise to surmount cancer drug resistance and/or synergize the effects of existing drugs.

• Language: English
• Keywords: cancer, drug resistance, aldo-keto reductases
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: Str. 1150-1171
• Numbering: Vol. 73, iss. 3
• PID: 20.500.12556/RUL-144716
• UDC: 615
• ISSN on article: 1521-0081
• DOI: 10.1124/pharmrev.120.000122
• COBISS.SI-ID: 67481603
• Publication date in RUL: 09.03.2023

Record is a part of a journal

• Title: Pharmacological reviews
• Shortened title: Pharmacol rev.
• Publisher: American Society for Pharmacology and Experimental Therapeutics
• ISSN: 1521-0081
• COBISS.SI-ID: 520791065

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: rak, odpornost na zdravila, aldo-keto reduktaze