Lactylation in cancer: Advances and opportunities for treatment resistance

IF 6.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-09-29 DOI:10.1002/ctm2.70478

Keke Xu, Yiyi Shou, Ruiqi Liu, Hao Xiong, Xiaomeng Dai, Xuanwen Bao, Xiaoyan Chen, Luanluan Huang, Hailong Sheng, Haibo Zhang, Yanwei Lu

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Abstract

Background

Lactylation, a recently identified post-translational modification that utilizes lactic acidas a substrate, has emerged as an important regulator of gene expression andprotein function. Since its discovery in 2019, lactylation has beenincreasingly recognized for its roles in cancer biology and treatment response.

Main text

Lactylationis strongly associated with tumor progression and malignancy, underscoring itspotential as a therapeutic target. Recent studies also link lactylation tocancer treatment resistance, suggesting that modulating this modification couldenhance therapeutic efficacy. As treatment resistance remains a major clinicalchallenge in oncology, accumulating evidence indicates that dysregulatedlactylation contributes to resistance across chemotherapy, immunotherapy, targeted therapy, and radiotherapy. Preclinical and clinical research has begunto delineate the molecular pathways through which lactylation shapes theseresistance processes, and experimental approaches targeting lactylation arebeing explored to restore therapeutic sensitivity.

Conclusion

This review systematically summarizes the mechanisms of lactylation and its roles intreatment resistance, highlighting the interplay between lactylation andtherapeutic response. We discuss current and emerging strategies that targetlactylation, providing a foundation for future therapeutic development aimed atovercoming resistance and improving cancer treatment outcomes.

Key points

Lactylation links glycolysis to tumor progression and therapeutic response.
Modulating lactylation writers and erasers restores treatment sensitivity.
Aberrant lactylation drives resistance tomultiple cancer therapies.
Crosstalk with other post-translational modifications suggests novel combination strategies.

Abstract Image

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癌症中的乳酸化：治疗耐药的进展和机会。

背景：乳酸化是最近发现的一种利用乳酸作为底物的翻译后修饰，已成为基因表达和蛋白质功能的重要调节因子。自2019年发现以来，乳酸化在癌症生物学和治疗反应中的作用越来越得到认可。乳酸酰化与肿瘤进展和恶性肿瘤密切相关，强调了其作为治疗靶点的潜力。最近的研究也将乳酸化与癌症治疗耐药性联系起来，表明调节这种修饰可以提高治疗效果。由于治疗耐药仍然是肿瘤学的主要临床挑战，越来越多的证据表明，乳酸化失调有助于化疗、免疫治疗、靶向治疗和放疗的耐药。临床前和临床研究已经开始描述乳酸化形成这些耐药过程的分子途径，并且正在探索针对乳酸化的实验方法以恢复治疗敏感性。结论：本文系统综述了乳酸化的机制及其在治疗耐药中的作用，重点介绍了乳酸化与治疗反应的相互作用。我们讨论了当前和新兴的靶向乙酰化的策略，为未来的治疗发展提供了基础，旨在克服耐药性和改善癌症治疗结果。重点：乳酸化将糖酵解与肿瘤进展和治疗反应联系起来。调节乳酸化写入器和擦除器恢复治疗敏感性。异常的乳酸化驱动多种癌症治疗的耐药性。具有其他翻译后修饰的相声提示了新的组合策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.