Cell Membrane Sialome: Sialic Acids as Therapeutic Targets and Regulators of Drug Resistance in Human Cancer Management

SIMPLE SUMMARY: The aberrant sialylation of membrane glycocalyx plays a pivotal role in the regulation of malignant cell behavior and correlates with a worse prognosis and shorter overall survival for patients. The biological and physical properties of sialome determine the negative charge and high hydrophilicity of cell membranes and thereby regulate cell–cell and cell–extracellular matrix interactions. There is increasing evidence that sialic acids influence cellular susceptibility in therapeutic management. Here, we focus on the engagement of sialic acids in chemoresistance and the potential effects of drugs and potential therapeutic agents on sialome-related machinery in malignant cells. ABSTRACT: A cellular sialome is a physiologically active and dynamically changing component of the cell membrane. Sialylation plays a crucial role in tumor progression, and alterations in cellular sialylation patterns have been described as modulators of chemotherapy effectiveness. However, the precise mechanisms through which altered sialylation contributes to drug resistance in cancer are not yet fully understood. This review focuses on the intricate interplay between sialylation and cancer treatment. It presents the role of sialic acids in modulating cell–cell interactions, the extracellular matrix (ECM), and the immunosuppressive processes within the context of cancer. The issue of drug resistance is also discussed, and the mechanisms that involve transporters, the tumor microenvironment, and metabolism are analyzed. The review explores drugs and therapeutic approaches that may induce modifications in sialylation processes with a primary focus on their impact on sialyltransferases or sialidases. Despite advancements in cellular glycobiology and glycoengineering, an interdisciplinary effort is required to decipher and comprehend the biological characteristics and consequences of altered sialylation. Additionally, understanding the modulatory role of sialoglycans in drug sensitivity is crucial to applying this knowledge in clinical practice for the benefit of cancer patients.