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REVIEW ARTICLE

Prominent cellular metabolic adaptations in pancreatic ductal adenocarcinoma tumor microenvironment

Silin Xiang1,2† ,  Shuai Sun2,3†* ,  Pan Zhao2,4† ,  Yanzhen Xu2,4,5 ,  Xu Mao2,4 ,  Xiaoying Tao2,4 ,  Junjun Du2,3 ,  Xiangyun He2,4 ,  Zhibo Zuo2,4 ,  Nan Li6* ,  Rongjing Zhou3*
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1 Graduate School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
2 Pathology Residency Training Base, Hangzhou First People’s Hospital, Westlake University, Hangzhou, Zhejiang, China
3 Department of Pathology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, China
4 Department of Pathology, Hangzhou First People’s Hospital, Westlake University, Hangzhou, Zhejiang, China
5 Department of Pathology, Hangzhou Geriatric Hospital, Hangzhou, Zhejiang, China
6 Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
†These authors contributed equally to this work.
EJMO, 026150164 https://doi.org/10.36922/EJMO026150164
Received: 10 April 2026 | Revised: 26 May 2026 | Accepted: 11 June 2026 | Published online: 8 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive cancer with a dismal prognosis and a 5-year survival rate of approximately 12%. The poor clinical outcomes are attributed to multiple factors, including difficulty in early detection, rapid metastasis, and intrinsic resistance to therapies. The tumor microenvironment of PDAC exhibits immunosuppressive features, nutrient-deprived conditions, and metabolic reprogramming. These factors collectively contribute to immune evasion and therapeutic resistance. Notably, metabolic reprogramming has emerged as a well-recognized hallmark of PDAC in both cancer cells and the surrounding milieu. Several key metabolic pathways are extensively rewired to support tumor growth, survival, and progression. In addition, accumulating evidence highlights critical metabolic crosstalk between cancer cells and various components of the TME, including cancer-associated fibroblasts, tumor-associated macrophages, tumor-associated neutrophils, regulatory T cells, and the intratumoral microbiota. These metabolic interactions profoundly influence tumor biological behavior and therapeutic response. We aim to provide a comprehensive synopsis of recent advances regarding cellular metabolic adaptations in the PDAC tumor microenvironment, including glycolysis, glutamine and lipid metabolism, macropinocytosis, and autophagy. We delineate the multiscale metabolic interplays within the tumor–stroma symbiosis and highlight promising therapeutic strategies targeting metabolic vulnerabilities. We also discuss energy metabolism-associated post-translational modifications, such as lysine lactylation and acetylation. In this review, we focus on metabolic interactions among tumor cells, anti-tumor cells, and immunosuppressive cells, with an emphasis on recent technological advances, including single-cell sequencing, spatial multi-omics, and artificial intelligence.

Keywords
Pancreatic ductal adenocarcinoma
Tumor microenvironment
Drug resistance
Metabolic reprogramming
Chemotherapy
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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