Protein modification systems as cancer biomarkers and therapeutic targets

Abstract Protein post-translational modifications (PTMs), such as acetylation, lactylation, methylation, phosphorylation, ubiquitination and glycosylation, play central roles in regulating diverse cellular processes, including signal transduction, metabolic adaptation, chromatin organization, and proteostasis. In cancer, PTM networks are extensively rewired, with profound alterations in enzyme levels, protein modification landscapes, and crosstalk among different modification types. These changes collectively shape key cancer hallmarks, such as sustained proliferative signaling, immune evasion, and therapeutic resistance. Recent advances in proteomic technologies have enabled comprehensive mapping of PTM landscapes and their regulatory mechanisms, facilitating the identification of PTM signatures associated with tumor subtyping, disease progression, and treatment response. This review summarized biomarkers and therapeutic targets associated with dysregulated PTM regulatory pathways in cancer.