Open Access

REVIEW

Lactylation in Cancer: Unlocking the Key to Drug Resistance and Therapeutic Breakthroughs

Xiangnan Feng^1,#, Dayong Li^2,#, Pingyu Wang¹, Xinyu Li², Guangyao Li^2,*

1 Clinical School of Medicine, Anhui Medical University, Hefei, 230022, China
2 Department of Gastrointestinal Surgery, The Second People’s Hospital of Wuhu, Wuhu, 241000, China

* Corresponding Author: Guangyao Li. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: New Insights in Drug Resistance of Cancer Therapy: A New Wine in an Old Bottle)

Oncology Research 2025, 33(11), 3327-3346. https://doi.org/10.32604/or.2025.067343

Received 30 April 2025; Accepted 27 June 2025; Issue published 22 October 2025

Abstract

Lactylation, a post-translational modification process that adds lactate groups to lysine residues, plays a crucial role in cancer biology, especially in drug resistance. However, the specific molecular mechanisms of lactylation in cancer progression and drug resistance are still unclear, and therapeutic strategies targeting the lactylation pathway are expected to overcome metabolic reprogramming and immune evasion. Therefore, this article provides a comprehensive description and summary of lactylation modification and tumor drug resistance. Numerous studies have shown that, due to the Warburg effect, there is an abnormally high level of lactate in tumor cells. Elevated levels of lactate promote metabolic reprogramming and alter key cellular processes, including gene expression, DNA repair, and immune regulation. These cellular processes are precisely the key factors for tumor cells to develop drug resistance. Lactylation also affects the tumor microenvironment, promoting immune evasion and resistance to immunotherapy in tumor cells. This modification affects proteins involved in metabolic pathways, glycolysis, and mitochondrial function, further supporting tumor growth and metastasis. Therefore, this article provides a comprehensive description and summary of lactylation modification and tumor drug resistance to clarify the specific mechanisms between the two and provide references and directions for future research on tumor drug resistance.

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