Novel anticancer drug discovery efforts targeting glycosylation: the emergence of fluorinated monosaccharides analogs

Introduction: Glycosylation is an essential enzymatic process of building glycan structures that occur mainly within the cell and gives rise to a diversity of cell surface and secreted glycoconjugates. These glycoconjugates play vital roles, for instance in cell-cell adhesion, interaction and communication, activation of cell surface receptors, inflammatory response and immune recognition. This controlled and well-coordinated enzymatic process is altered in cancer, leading to the biosynthesis of cancer-associated glycans, which impact glycan-dependent biological roles.

Areas covered: In this review, the authors discuss the importance of targeting cancer-associated glycans through potent glycan biosynthesis inhibitors. It focuses on the use of analogs, providing an overview of findings involving these in cancer. The highly explored fluorinated monosaccharide analogs targeting aberrant glycosylation are described, aiming to inspire advances in the field.

Expert opinion: Altered glycosylation, such as increased sialylation and fucosylation, is a feature in cancer and has been shown to play key roles in several malignant properties of cancer cells. Strategies aiming at remodeling cancer cells´ glycome are emerging and present a huge potential for cancer therapy. Fluorinated monosaccharides have been gathering promising pre-clinical results as novel cancer drugs. Nevertheless, cancer specific targeting strategies must be considered to avoid significant side-effects.