Cell surface fucose ablation as a therapeutic strategy for malignant neoplasms

Abstract

The sugar alpha-L-fucose is overexpressed in many human malignancies, especially on specific glycoproteins, glycolipids, certain mucins, and putative cell adhesion ligands found on cancer cell surfaces. Many of these molecules are known or suspected mediators of cell-cell adhesion, cell signaling, motility, or invasion. As knowledge of fucose metabolism evolves and specific mechanisms of its distribution and incorporation are more exactly documented, modulation of fucose expression in cancer is becoming increasingly more feasible. The authors propose that cancer cell surface alpha-L-fucose is a logical target for selective therapeutic ablation. Reduction of fucose content on the surfaces of malignant cells should effectively cripple the cells' physiologic functions by altering or dysregulating cell-cell or cell-matrix interactions, critical for maintaining the malignant phenotype. Significant therapeutic benefits might include modulation of adhesion abnormalities in the cancer cells, reduction of cancer cell motility or invasiveness, reexposure to immune surveillance, or a combination of these events.