In Search for Inhibitors of Human Aldo-Keto Reductase 1B10 (AKR1B10) as Novel Agents to Fight Cancer and Chemoresistance: Current State-of-the-Art and Prospects

Aldo-keto reductase 1B10 (AKR1B10) is a human enzyme that catalyzes the NADPH-dependent reduction of several different carbonyl compounds to the corresponding alcohols. Under physiological conditions, AKR1B10 is expressed mainly in the gastrointestinal tract, where it can detoxify reactive carbonyl compounds derived from dietary sources and xenobiotics. AKR1B10 is highly expressed in several cancers and precancerous conditions, proving to be crucially implicated in carcinogenesis and to function as a prognostic indicator of tumor development. Moreover, AKR1B10 up-regulation is strictly related to acquired resistance to known anticancer drugs. High levels of this enzyme are also correlated to the pathogenesis of noncancerous diseases, such as skin pathologies and COVID-19 complications. Therefore, in the last two decades, AKR1B10 has attracted interest as a novel target for agents able to fight both cancer and chemoresistance, and here, it is explored from a medicinal chemistry perspective.