Hu ZY, Ding D, Song Y, Deng YF, Zhang CM, Yu T. Molecular mechanism of pancreatic ductal adenocarcinoma: The heterogeneity of cancer-associated fibroblasts and key signaling pathways. World J Clin Oncol 2025; 16(2): 97007 [DOI: 10.5306/wjco.v16.i2.97007]
Corresponding Author of This Article
Tao Yu, MS, Chief Doctor, Digestive Department I, Shaanxi Provincial Hospital of Traditional Chinese Medicine, No. 4 Ming Palace Road, Lianhu District, Xi’an 710000, Shaanxi Province, China. yt0745@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
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/
Zhong-Yuan Hu, Ding Ding, First School of Clinical Medicine, Shaanxi University of Chinese Medicine, Xianyang 712000, Shaanxi Province, China
Yu Song, College of Acupuncture and Massage, Shaanxi University of Chinese Medicine, Xianyang 712000, Shaanxi Province, China
Ya-Feng Deng, Graduate School, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China
Cheng-Ming Zhang, Tao Yu, Digestive Department I, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an 710000, Shaanxi Province, China
Co-first authors: Zhong-Yuan Hu and Ding Ding.
Author contributions: Hu ZY and Ding D designed and finalized the overall structure of the manuscript; Song Y, Deng YF and Zhang CM played a significant role in the discussion and design of the manuscript; Yu T was responsible for writing, editing, and conducting the literature review. Hu ZY and Ding D contributed equally to this work as co-first authors.
Supported by National Key Research and Development Program Project, No. 2017YFC1700601; Shaanxi Provincial Key Research and Development Program Project, No. 2018SF-350; and Leading Talents in Scientific and Technological Innovation of the Shaanxi Province Special Support Plan, No. 00518.
Conflict-of-interest statement: None of the authors have any relevant conflicts of interest to disclose concerning this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tao Yu, MS, Chief Doctor, Digestive Department I, Shaanxi Provincial Hospital of Traditional Chinese Medicine, No. 4 Ming Palace Road, Lianhu District, Xi’an 710000, Shaanxi Province, China. yt0745@163.com
Received: May 20, 2024 Revised: October 4, 2024 Accepted: November 4, 2024 Published online: February 24, 2025 Processing time: 204 Days and 19.1 Hours
Abstract
Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis, leading to a notably low five-year survival rate. This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers, such as mutations in CDKN2A, KRAS, SMAD4, and TP53, along with the influence of cancer-associated fibroblasts (CAFs) on disease progression. In particular, we focused on the pivotal roles of signaling pathways such as the transforming growth factor-β and Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies. This study provides new scientific perspectives on pancreatic cancer treatment, especially in the development of precision medicine and targeted therapeutic strategies, and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens. Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.
Core Tip: This research explored the mechanisms of action of fibroblasts in pancreatic tumors and revealed their effects on the tumor microenvironment. This study revealed that fibroblasts enhance tumor growth and metastasis through specific signaling pathways, suggesting that targeting fibroblasts may emerge as a new strategy for treating pancreatic cancer.
