Implications and mechanisms of O-GlcNAcylation in cancer therapy resistance

O-linked-N-acetylglucosaminylation (O-GlcNAcylation), one of the protein post-translational modifications, is the process of adding O-linked-beta-D-N-acetylglucosaminylation (O-GlcNAc) to serine and threonine residues of proteins. O-GlcNAcylation regulates various fundamental cell biological processes, including gene transcription, signal transduction, and cellular metabolism. The role of dysregulated O-GlcNAcylation in tumorigenesis has been recognized, but its role in cancer therapy tolerance has not been elucidated. Therefore, this paper provides the latest evidence on the role of O-GlcNAcylation in cancer therapy responsiveness to understand the impact of O-GlcNAcylation on cancer therapy outcomes, as well as analyzing several possible mechanisms by which O-GlcNAcylation dysregulation affects cancer therapy efficacy, and discusses the possibility of O-GlcNAcylation as a cancer therapy sensitizer.