Aberrant Sialylation in Cancer: Therapeutic Opportunities

SIMPLE SUMMARY: All cells are covered in a thick layer of sugar molecules known as glycans. Changes to this sugar coat are common in cancer, and in particular cancer cells often display high levels of a glycan known as sialic acid. Sialic acid glycans play important roles in cancer biology and can help tumours grow, spread to other sites, and evade the immune system. Strategies to target sialic acid are being actively investigated and hold huge potential for cancer research. Here, I outline why sialic acid is so important in cancer, discuss recent advances in this field, and highlight opportunities for the development of new sialic acid targeting therapies. ABSTRACT: The surface of every eukaryotic cell is coated in a thick layer of glycans that acts as a key interface with the extracellular environment. Cancer cells have a different ‘glycan coat’ to healthy cells and aberrant glycosylation is a universal feature of cancer cells linked to all of the cancer hallmarks. This means glycans hold huge potential for the development of new diagnostic and therapeutic strategies. One key change in tumour glycosylation is increased sialylation, both on N-glycans and O-glycans, which leads to a dense forest of sialylated structures covering the cell surface. This hypersialylation has far-reaching consequences for cancer cells, and sialylated glycans are fundamental in tumour growth, metastasis, immune evasion and drug resistance. The development of strategies to inhibit aberrant sialylation in cancer represents an important opportunity to develop new therapeutics. Here, I summarise recent advances to target aberrant sialylation in cancer, including the development of sialyltransferase inhibitors and strategies to inhibit Siglecs and Selectins, and discuss opportunities for the future.