Abstract

Lactylation, a novel metabolite-derived post-translational modification, has emerged as a pivotal mechanism bridging dysregulated metabolism and oncogenic signaling in breast cancer. This review comprehensively synthesizes current knowledge on the molecular mechanisms, pathophysiological roles, and therapeutic implications of lactylation in breast cancer. Driven by the glycolytic tumor microenvironment, lactate serves as a substrate for lactylation on both histone and non-histone proteins. Histone lactylation alters chromatin landscape to promote the expression of genes critical for proliferation, metastasis, and immunosuppression. Furthermore, lactylation of key non-histone proteins, such as metabolic enzymes and signaling molecules, rewires cellular pathways to enhance tumorigenesis. Accumulating evidence demonstrates that lactylation contributes significantly to breast cancer progression, drug resistance and immune evasion, underscoring its role as an active driver rather than a passive consequence of tumor metabolism. Targeting the lactylation pathway therefore represents a promising therapeutic strategy. This review consolidates the understanding of lactylation’s function in breast cancer pathobiology, highlights its potential as a prognostic biomarker and therapeutic target, and discusses future research directions for clinical translation. Ultimately, deciphering the lactylation code opens new avenues for overcoming therapy resistance and improving patient outcomes in breast cancer.

Keywords:Lactylation; Breast cancer; Warburg effect; Tumor microenvironment; Therapeutic target