The Dysregulation of Lysine Acetylation in Esophageal Squamous Cell Carcinoma: Mechanisms, Therapeutic Targets and Clinical Perspectives.

Esophageal cancer is a type of malignant tumor with high incidence and mortality rates worldwide, and esophageal squamous cell carcinoma (ESCC) is the predominant pathological subtype in China. Despite continuous advancements in treatment methods, the prognosis of ESCC patients remains poor and there is an urgent need to develop new therapeutic strategies. Recent epigenetic frontiers have identified the dysregulation of lysine acetylation, a dynamic and reversible post-translational modification, as a pivotal driver of ESCC pathogenesis. This process is orchestrated by a dynamic interplay between "writers" (lysine acetyltransferases, KATs), "erasers" (lysine deacetylases, KDACs), and "readers". In this review, we systematically delineate the molecular landscape of lysine acetylation in ESCC and emphasize how these epigenetic modulators reshape the transcriptional program of tumor cells. Specifically, we highlight the oncogenic or tumor-suppressive roles of key acetylating enzymes and their non-histone substrates, which bridge the gap between epigenetic alterations and malignant phenotype. And we summarize the latest research progress and clinical application potential of KAT inhibitors (KATi), KDAC inhibitors (KDACi), and inhibitors of lysine acetylation readers in various tumor. Additionally, we discuss the challenges of drug resistance in epigenetic therapy and opportunities in targeting acetylation modification. By providing a comprehensive synthesis of the acetylation-ESCC axis, this review aims to offer theoretical guidance for the development of novel epigenetic biomarkers and targeted interventions to improve the prognosis of ESCC patients.