Aldo-keto reductases and cancer drug resistance

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

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.

• Jezik: Angleški jezik
• Ključne besede: cancer, drug resistance, aldo-keto reductases
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: Str. 1150-1171
• Številčenje: Vol. 73, iss. 3
• PID: 20.500.12556/RUL-144716
• UDK: 615
• ISSN pri članku: 1521-0081
• DOI: 10.1124/pharmrev.120.000122
• COBISS.SI-ID: 67481603
• Datum objave v RUL: 09.03.2023

Gradivo je del revije

• Naslov: Pharmacological reviews
• Skrajšan naslov: Pharmacol rev.
• Založnik: American Society for Pharmacology and Experimental Therapeutics
• ISSN: 1521-0081
• COBISS.SI-ID: 520791065

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: rak, odpornost na zdravila, aldo-keto reduktaze