Carbohydrate- and heterocycle-based β-glucocerebrosidase inhibitors: State of the art and emerging relationship with cancer treatment

Overcoming drug resistance remains a significant challenge in cancer treatment. The enzyme β-glucocerebrosidase (GCase) plays several roles in cellular processes, including carbohydrate metabolism and the hydrolysis of glucosides. Aberrant GCase activity has been linked to various diseases, and recent studies have implicated it in cancer, where increased levels of GCase are frequently observed. This Review examines the relationship between GCase and cancer, emphasizing its potential as a therapeutic target. Inhibitors with diverse chemical structures, ranging from carbohydrate-based to non-carbohydrate-based compounds, exhibit varying levels of specificity for GCase over other glycosidases. Understanding the selectivity of these inhibitors is crucial for advancing therapeutic strategies. By examining the complex interplay between GCase, cancer, and inhibitor development, this Review aims to provide a foundation for future research and innovative therapeutic approaches in oncology.