Emerging Roles of Carbohydrates and Glycomimetics in Anticancer Drug Design

Joseph   J.   Barchi Jr.

doi:10.2174/1381612003400876

Abstract

Tumorigenesis is accompanied by marked changes in the expression and presentation of various macromolecules at the cell surface. These tumor-associated adjustments result from the differential expression of genes coding for the production or post-translational modifications of these macromolecules during transformation to a particular tumor phenotype. In turn, tumor cells acquire distinct biophysical properties which set them apart from their normal counterparts. Alterations of carbo-hydrate structures and their organization on the surface of neoplastic cells is a hallmark of the tumorigenic and, most notably, the metastatic phenotype. Carbohydrate-protein and carbohydrate-carbohydrate interactions are critical events in the progression, dissemination and invasion of cancer cells. Many cell-cell contacts and subsequent remodeling of the tumor microenvironment are mediated by cell-surface glycans. The discovery of agents that modulate these interactions or interfere with the processing of tumor associated oligosaccharides is a fervent area of research today. This review will highlight the current status of the use of carbohydrate-based compounds that are being evaluated as potential anticancer therapeutics. In addition, the use of structures based on glycopeptides and carbohydrate mimetics will also be discussed.

Keywords: carbohydrates and glycomimetics, anti cancer drug, glycoprocessing enzymes, glycosidase inhibitors, tumor vaccine design, Tn and Sialyl Tn and Tf, glycolipid based, polysacchrides and BRM, CD44 and Hyaluronan