20.500.12556/RUL-144716 Aldo-keto reductases and cancer drug resistance 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. cancer drug resistance aldo-keto reductases rak odpornost na zdravila aldo-keto reduktaze true false true Angleški jezik Slovenski jezik Članek v reviji 2023-03-09 09:18:09 2023-03-09 09:18:10 2023-03-10 03:35:48 0000-00-00 00:00:00 2021 0 0 Str. 1150-1171 iss. 3 Vol. 73 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615 1521-0081 10.1124/pharmrev.120.000122 67481603 1150.full.pdf 1150.full.pdf 1 0861C30D7EC43D0CE2F52F98F9C4E1E3 cc810faa9b93420a9f76e4a39e05b172dbd0f1102922cbf0492dd9aef3c05b92 09ca4528-be53-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167187 https://pharmrev.aspetjournals.org/content/73/3/1150 0 ff4ac038-be52-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167186 Medicinska fakulteta 0 0 0