Sialic acid residue on tumor cell

Sialic acid residues are a family of nine-carbon acidic sugars that frequently cap the outer ends of glycan chains on cell-surface glycoproteins and glycolipids[1][2][7]. Tumor cells typically display increased sialylation ("hypersialylation") due to upregulated sialyltransferase activity and altered glycan metabolism, resulting in excess negatively charged sialic acid on the cell surface[1][2][4][5]. This abnormal glycan pattern facilitates immune evasion (through interaction with immune-inhibitory Siglec receptors), promotes tumor proliferation, enhances cell adhesion and motility, increases resistance to apoptosis, and is associated with chemotherapy and radiotherapy resistance[2][4][5][6]. Because of their essential role in cancer cell survival, metastasis, and immune escape, sialic acid residues on tumor cells—especially certain hypersialylated glycan epitopes—are considered promising and actively investigated therapeutic targets in oncology[3][4]. Therapies aiming to block, remove, or mask these residues (e.g., with sialic acid mimetics, glycosidases, or antibody-based strategies) are in preclinical and early clinical stages and present opportunities for novel cancer immunotherapies but pose challenges in specificity and immune-related adverse effects due to the widespread physiological roles of sialic acid residues[4][5][6].

Other names

Sialylated glycanHypersialylated glycanTumor-associated sialic acidTumor cell sialylation

Blockade of sialic acid-binding to Siglec receptors disables tumor immune evasion, allowing cytotoxic T cell and NK cell responses; Inhibition or enzymatic removal of sialic acid residues disrupts protective tumor glycocalyx, promoting immune recognition and cell death; Targeting sialyltransferases reduces hypersialylation, suppressing metastatic phenotypes and therapy resistance