Li X, Jiao Y, Liu YH. Precision medicine advances in pancreatic cancer driven by genomic and molecular alterations. World J Gastrointest Oncol 2025; 17(11): 111264 [DOI: 10.4251/wjgo.v17.i11.111264]
Corresponding Author of This Article
Ya-Hui Liu, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun 130021, Jilin Province, China. yahui@jlu.edu.cn
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Gastroenterology & Hepatology
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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/
Nov 15, 2025 (publication date) through Nov 13, 2025
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World Journal of Gastrointestinal Oncology
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1948-5204
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Li X, Jiao Y, Liu YH. Precision medicine advances in pancreatic cancer driven by genomic and molecular alterations. World J Gastrointest Oncol 2025; 17(11): 111264 [DOI: 10.4251/wjgo.v17.i11.111264]
World J Gastrointest Oncol. Nov 15, 2025; 17(11): 111264 Published online Nov 15, 2025. doi: 10.4251/wjgo.v17.i11.111264
Precision medicine advances in pancreatic cancer driven by genomic and molecular alterations
Xiang Li, Yan Jiao, Ya-Hui Liu
Xiang Li, Department of First Operation Room, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Yan Jiao, Ya-Hui Liu, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Li X wrote the initial draft; Jiao Y contributed to the study design and literature review; Liu YH contributed to the study design, help to design the study and revisions to the final manuscript. All authors approved the final version to be published.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for 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: Ya-Hui Liu, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun 130021, Jilin Province, China. yahui@jlu.edu.cn
Received: June 26, 2025 Revised: July 13, 2025 Accepted: September 24, 2025 Published online: November 15, 2025 Processing time: 141 Days and 0.2 Hours
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies with limited treatment efficacy. Advances in precision oncology, enabled by next-generation sequencing, have highlighted key molecular targets. Kirsten rat sarcoma viral oncogene homolog mutations, present in up to 90% of cases, drive aggressive biology, though most variants remain undruggable; allele-specific inhibitors and exosome-based RNA interference are under exploration. Breast cancer susceptibility gene 1/2 mutations occur in 4%-7% of patients, conferring sensitivity to platinum agents and poly(ADP-ribose) polymerase inhibitors. Other rare but actionable alterations - such as v-raf murine sarcoma viral oncogene homolog B1 (V600), neurotrophic tyrosine receptor kinase, fibroblast growth factor receptor 2, and RET fusions - show benefit in tumor-agnostic trials, broadening options for selected subgroups. Immunotherapy is limited, as high tumor mutational burden and mismatch repair deficiency are uncommon in PDAC, though predictive when present. Co-mutations in tumor protein p53, cyclin-dependent kinase inhibitor 2A, and SMAD4 further stratify prognosis and influence therapy response. Cross-cancer analyses underscore the necessity of PDAC-specific strategies despite shared genomic drivers. Collectively, these insights support routine germline and somatic testing, enrollment in biomarker-matched trials, and rational combination strategies, establishing molecular profiling as central to advancing precision treatment in pancreatic cancer.
Core Tip: This review highlights the transformative impact of precision medicine in pancreatic ductal adenocarcinoma by focusing on clinically relevant genomic and molecular alterations such as Kirsten rat sarcoma viral oncogene homolog and breast cancer susceptibility gene mutations, rare actionable fusions, and co-mutational signatures. It emphasizes the importance of integrating routine molecular profiling into clinical workflows to guide targeted therapies and personalized treatment strategies.
