Cell surface fucose ablation as a therapeutic strategy for malignant neoplasms

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