Protein lactylation, an emerging post-translational modification, is providing new insights into tumor biology and challenging our current understanding of cancer mechanisms. Our review illuminates the intricate roles of lactylation in carcinogenesis, tumor progression, and therapeutic responses, positioning it as a critical linchpin connecting metabolic reprogramming, epigenetic modulation, and treatment outcomes. We provide an in-depth analysis of lactylation's molecular mechanisms and its far-reaching impact on cell cycle regulation, immune evasion strategies, and therapeutic resistance within the complex tumor microenvironment. Notably, this review dissects the paradoxical nature of lactylation in cancer immunotherapy and radiotherapy. While heightened lactylation can foster immune suppression and radioresistance, strategically targeting lactylation cascades opens innovative avenues for amplifying the efficacy of current treatment paradigms. We critically evaluate lactylation's potential as a robust diagnostic and prognostic biomarker and explore frontier therapeutic approaches targeting lactylation. The synergistic integration of multi-omics data and artificial intelligence in lactylation research is catalyzing significant strides towards personalized cancer management. This review not only consolidates current knowledge but also charts a course for future investigations. Key research imperatives include deciphering tumor-specific lactylation signatures, optimizing synergistic strategies combining lactylation modulation with immune checkpoint inhibitors and radiotherapy, and comprehensively assessing the long-term physiological implications of lactylation intervention. As our understanding of lactylation's pivotal role in tumor biology continues to evolve, this burgeoning field promises to usher in transformative advancements in cancer diagnosis, treatment modalitie.
Keywords: Immunotherapy; Lactylation; Metabolic Reprogramming; Radiotherapy.
Copyright © 2025. Published by Elsevier B.V.