Emerging Acylations in Malignancies: Molecular Mechanisms, Research Advances, and Clinical Implications

Cancer is among the leading causes of death worldwide, and its development has been a consistent focus of research. Many investigations have demonstrated the close relationship between epigenetic mechanisms and cancer development. Posttranslational modifications (PTMs) are pivotal regulators of cancer biology, orchestrating protein functional diversity, epigenetic reprogramming, and metabolic adaptation to drive tumor initiation and progression.In addition to classical phosphorylation and acetylation, advancements in mass spectrometry have led to the discovery of more forms of protein modification. These modifications bridge metabolic dysregulation and oncogenic reprogramming. In this review, we summarize current knowledge on the molecular mechanisms underlying nine novel acylations in cancer, including the roles of acyltransferases, deacylases, and metabolic enzymes in generating acyl-CoA donors. We highlight preclinical and clinical evidence linking aberrant acylation to cancer progression, with a focus on emerging therapeutic strategies targeting acylation enzymes and their combination with immunotherapy or metabolic interventions. Key research gaps are identified, including the need for high-resolution profiling of acylation dynamics, tissue-specific biomarkers, and mechanistic studies on rare types of acylation. By integrating basic research and translational insights, this review highlights the translational potential of novel types of acylation as both a prognostic marker and a therapeutic target in precision oncology.