Crosstalk between acetylation modification and autophagy in cancer: roles, mechanisms, and therapeutic potential

Acetylation modification and autophagy are fundamental mechanisms regulating cell fate and homeostasis, exhibiting a highly coordinated and dynamic interplay in cancer development. Emerging studies have revealed that acetylation modulates the activation and inhibition of autophagy by regulating the activity, stability, and subcellular localization of autophagy-related proteins. Conversely, autophagy reciprocally influences cellular acetylation levels through selective degradation of acetyltransferases and deacetylases, as well as modulation of acetyl-CoA metabolism, forming a complex bidirectional regulatory network. In cancer, this crosstalk critically contributes to metabolic reprogramming, migration and invasion, therapeutic resistance, and adaptation to the tumor microenvironment, thereby influencing tumor progression and prognosis. This review systematically summarizes the functional roles and interaction mechanisms of acetylation and autophagy across various cancer types, with a particular focus on small-molecule agents targeting this axis and their current status in clinical applications. Although these therapeutic strategies have demonstrated promising anti-tumor potential in both preclinical and clinical settings, challenges such as limited drug specificity, mechanistic heterogeneity, and acquired resistance remain to be addressed. Future research should explore non-canonical forms of acetylation, immune regulation within the tumor microenvironment, and personalized therapeutic models, aiming to identify key regulatory nodes in the acetylation-autophagy network and unlock their potential for precision cancer therapy.