Glycosylation pathways as drug targets for cancer: glycosidase inhibitors
The combined and ordered sequential action of glycosidases and glycosyltransferases in mammalian cell compartments leads to the addition of defined glycans to proteins and lipids. Altered glycosylation patterns, neoexpression, underexpression or overexpression of glycans are a hallmark of cancer. These changes are either found in the core or the terminal structures of the carbohydrates of glycoproteins. Affected proteins can be either cellular, cell-surface or secreted proteins, and glycosylation modifications frequently result in a modified expression, metabolism, functions, properties, stability and/or cellular localization of glycoproteins in cancer cells, resulting in part in their uncontrolled growth and aggressive behavior. Therefore glycosylation pathways, and the glycosidases and glycosyltransferases of these pathways, represent potential innovative modalities for drug development in cancer therapies which are just beginning to be explored. This review proposes to summarize the published information for glycosidases and their inhibitors in cancer.