Hawanga GD, Li ZX, Li MX, Zhang XL, Qian DH. Lactylation in pancreatic cancer: From molecular mechanisms to therapeutic perspectives. World J Clin Oncol 2026; 17(3): 115882 [DOI: 10.5306/wjco.v17.i3.115882]
Corresponding Author of This Article
Dao-Hai Qian, MD, PhD, Associate Chief Physician, Associate Professor, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu 241001, Anhui Province, China. 20161106@wnmc.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Mar 24, 2026 (publication date) through Mar 26, 2026
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Journal Information of This Article
Publication Name
World Journal of Clinical Oncology
ISSN
2218-4333
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Hawanga GD, Li ZX, Li MX, Zhang XL, Qian DH. Lactylation in pancreatic cancer: From molecular mechanisms to therapeutic perspectives. World J Clin Oncol 2026; 17(3): 115882 [DOI: 10.5306/wjco.v17.i3.115882]
Gabriel Dickson Hawanga, Zhao-Xing Li, Mao-Xin Li, Xiu-Lei Zhang, Dao-Hai Qian, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui Province, China
Author contributions: Hawanga GD conceived the idea and designed the manuscript; Hawanga GD and Li ZX critically revised the manuscript for important intellectual content; Li MX, Zhang XL, and Qian DH collected the literature and drafted the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Dao-Hai Qian, MD, PhD, Associate Chief Physician, Associate Professor, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu 241001, Anhui Province, China. 20161106@wnmc.edu.cn
Received: October 29, 2025 Revised: November 23, 2025 Accepted: January 12, 2026 Published online: March 24, 2026 Processing time: 146 Days and 18.9 Hours
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by intense metabolic reprogramming and an immunosuppressive tumor microenvironment. The recent discovery of lactylation, a novel post-translational modification derived from lactate, provides a direct molecular link between glycolysis and the regulation of gene expression. This review synthesizes the emerging role of lactylation in PDAC pathogenesis. We detail how a lactate-rich microenvironment fuels the lactylation of histones and non-histone proteins, driving oncogenic processes such as transcriptional reprogramming, maintenance of lineage plasticity, and therapeutic resistance. Furthermore, lactylation in stromal and immune cells reinforces immunosuppression, facilitating tumor progression. We critically evaluate the translational potential of targeting this axis through inhibitors of lactate production, transport, or the epigenetic writers themselves. While promising, these strategies face significant challenges, including achieving molecular specificity and overcoming drug delivery barriers in PDAC. We conclude that lactylation represents a critical metabolic-epigenetic link in PDAC and a compelling therapeutic target worthy of further investigation.
Core Tip: This mini-review highlights lactylation, a lactate-derived epigenetic modification, as a pivotal mechanism linking the intense glycolytic metabolism of pancreatic ductal adenocarcinoma to its aggressive phenotype. We synthesize how lactylation of histones and non-histone proteins drives oncogenic transcription, chemoresistance, and immune suppression. The article critically evaluates the promise of targeting lactylation “writers” and “erasers”, lactate transporters, and metabolic enzymes for therapy, while also discussing the challenges of specificity, drug delivery, and biomarker validation that must be addressed to translate these strategies to the clinic.
