Yu Danqing, Zhong Qingping, Wang Yanlin, Yin Chang, Bai Minghua, Zhu Ji, Chen Jinggang, Li Huaming, Hong Weifeng
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310000, China.
Ageing Res Rev. 2025 Feb;104:102670. doi: 10.1016/j.arr.2025.102670. Epub 2025 Jan 24.
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.
蛋白质乳酰化是一种新兴的翻译后修饰,它为肿瘤生物学提供了新的见解,并挑战了我们目前对癌症机制的理解。我们的综述阐明了乳酰化在致癌作用、肿瘤进展和治疗反应中的复杂作用,将其定位为连接代谢重编程、表观遗传调控和治疗结果的关键枢纽。我们深入分析了乳酰化的分子机制及其在复杂肿瘤微环境中对细胞周期调控、免疫逃逸策略和治疗抗性的深远影响。值得注意的是,本综述剖析了乳酰化在癌症免疫治疗和放射治疗中的矛盾性质。虽然乳酰化增强可促进免疫抑制和放射抗性,但战略性地靶向乳酰化级联反应为提高当前治疗模式的疗效开辟了创新途径。我们批判性地评估了乳酰化作为一种强大的诊断和预后生物标志物的潜力,并探索了靶向乳酰化的前沿治疗方法。多组学数据和人工智能在乳酰化研究中的协同整合正在推动个性化癌症管理取得重大进展。本综述不仅巩固了当前的知识,还为未来的研究指明了方向。关键的研究重点包括破译肿瘤特异性乳酰化特征、优化将乳酰化调节与免疫检查点抑制剂和放射治疗相结合的协同策略,以及全面评估乳酰化干预的长期生理影响。随着我们对乳酰化在肿瘤生物学中关键作用的理解不断发展,这个新兴领域有望在癌症诊断、治疗方式上带来变革性进展。