Emerging role of histone and non-histone lactylation in metabolic reprogramming of female-specific malignancies

Lysine lactylation (Klac), a recently characterized post-translational modification, has emerged as a critical epigenetic regulator in female-prevalent malignancies including breast, ovarian, cervical, and endometrial cancers. Emerging evidence from recent studies demonstrates that both histone and non-histone Klac modifications exert oncogenic effects through multifaceted mechanisms: orchestrating transcriptional reprogramming, redirecting metabolic flux, reshaping immune microenvironments, and potentiating malignant phenotypes in cellular proliferation, migration, and invasion. The dynamic landscape of Klac patterns shows promise as a dual-purpose biomarker platform, potentially enabling both early detection and prognostic stratification in these hormone-related malignancies. Current investigations further highlight therapeutic opportunities through targeting Klac-associated pathways, particularly in developing precision interventions against therapy-resistant tumor subtypes. This comprehensive review meticulously scrutinizes the expression profiles, functional ramifications, and molecular interactions within histone and non-histone protein Klac networks in breast and gynecological cancers, while rigorously assessing their translational potential. Future investigations should prioritize three critical standardizing lactylation detection methodologies for clinical specimens and elucidating its systems-level interplay with other epigenetic regulators. Concurrently, rigorous preclinical validation of Klac-targeting compounds remains imperative to propel therapeutic innovation.