Aldo-keto reductase family 1 member B10 and Aldo-keto reductase family 1 member C2 (AKR1B10/AKR1C2)

Aldo-keto reductase family 1 member B10 (AKR1B10) and Aldo-keto reductase family 1 member C2 (AKR1C2) are distinct enzymes belonging to the aldo-keto reductase (AKR) superfamily of NADPH-dependent oxidoreductases. AKR1B10 is primarily involved in the metabolism of retinals to retinols, the detoxification of reactive aldehydes such as 4-hydroxy-2-nonenal, and the regulation of lipid synthesis through its interaction with acetyl-CoA carboxylase. It is frequently overexpressed in several cancers, including hepatocellular carcinoma and non-small cell lung cancer, where it promotes tumor survival and resistance to anthracyclines. AKR1C2, also known as 3-alpha-hydroxysteroid dehydrogenase type 3, plays a critical role in steroid metabolism by inactivating 5-alpha-dihydrotestosterone (DHT) and is implicated in hormone-dependent cancers and chemoresistance. These two enzymes are often discussed together as they are co-upregulated in specific pathological contexts, such as Barrett's esophagus and various drug-resistant malignancies, contributing to the metabolic reprogramming of cancer cells. Targeting both AKR1B10 and AKR1C2 with small-molecule inhibitors represents a therapeutic strategy to overcome chemoresistance and inhibit tumor progression by disrupting the detoxification of drugs and the production of pro-tumorigenic metabolites.

Other names

AKR1B10AKR1C2ALDRL1ARL-1HSIDD2BABP3-alpha-HSD3Aldo-keto reductase family 1 member B10Aldo-keto reductase family 1 member C2

Inhibition of NADPH-dependent oxidoreductase activity to block the detoxification of chemotherapeutic agents and the production of pro-tumorigenic metabolites.