L-Fucose: a dietary sugar with multifaceted potential in the biology and therapy of cancer.

Fucosylation, the conjugation of glycoproteins and glycolipids with the dietary sugar L-fucose, can have key functional and regulatory roles across a range of normal biological and developmental processes. Although the full repertoire of fucosylated proteins and their direct influence on signalling and cellular behaviour remains incompletely understood, it is not surprising that deregulated fucosylation has been increasingly associated with disease contexts, particularly cancer. Importantly, fucosylation regulates the biology of immune and other stromal cells, and emerging studies have elucidated how pathological aberrations in fucosylation can deregulate signalling that governs cellular interactions in the tumour microenvironment, thereby influencing tumour progression and therapeutic responses. Accordingly, fucosylated glycoproteins and glycans have been reported to exhibit potential biomarker utility, associating with cancer type and staging. Notably, fucosylation appears to be therapeutically actionable, as simply administering L-fucose orally can suffice to suppress tumour growth and stimulate antitumour immune responses in preclinical models. However, given that the blockade of fucosylation machinery can elicit similar antitumour effects reflects the diversity of cell-intrinsic and cell-extrinsic roles that fucosylation can divergently have across the tumour microenvironment. Here, we review recent glycobiology discoveries that shed light on the complexity of fucosylation, its mechanistic roles in immune and tumour biology, and how it might be strategically leveraged for the treatment of cancer.