Review
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2025; 17(7): 103337
Published online Jul 15, 2025. doi: 10.4251/wjgo.v17.i7.103337
Importance of landscape exploration and progress in molecular therapies and precision medicine for pancreatic ductal adenocarcinoma
Maher Hendi, Bin Zhang, Yi-Ping Mou, Xiu-Jun Cai
Maher Hendi, Bin Zhang, Department of General Surgery, Zhejiang University School of Medicine Affiliated Sir Run Run Shaw Hospital, Hangzhou 310029, Zhejiang Province, China
Yi-Ping Mou, Department of General Surgery, Zhejiang Provincial People’s Hospital, Hangzhou 310016, Zhejiang Province, China
Xiu-Jun Cai, Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, Zhejiang Province, China
Author contributions: Hendi M and Zhang B contributed equally to this manuscript as co-first authors of this article. Hendi M, Zhang B, Mou YP, and Cai XJ drafted the manuscript and revised the manuscript. All authors have read and approved the final manuscript.
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: Xiu-Jun Cai, MD, PhD, Chief Physician, FACS, FRCS, President, Professor, Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, No. 3 Qingchun Road, Hangzhou 310016, Zhejiang Province, China. srrs_cxj@zju.edu.cn
Received: November 18, 2024
Revised: March 19, 2025
Accepted: March 20, 2025
Published online: July 15, 2025
Processing time: 241 Days and 5 Hours
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a global health challenge and remains one of the most lethal malignancies; there are only a few therapeutic options. However, significant efforts have led to the identification of major genetic factors that drive the progression and pathogenesis of PDAC. Notably, the research and application of molecular targeted therapies and immunotherapies have rapidly increased and facilitated great progress in the treatment of many malignant tumors, additional targeted therapies and immunotherapy based on next-generation sequencing results provide new opportunities for the diagnosis and treatment of pancreatic tumors. Immune checkpoint inhibitors are also now being incorporated as PDAC therapies, and combinations of molecularly targeted therapies with immunotherapies are emerging as strategies for boosting the immune response. The investigation of biomarkers of a response or primary resistance to immunotherapies is also an emerging research area. Herein, we further discuss the recent technological advances that continue to expand our understanding of PDAC complexity. We discuss the advancements expected in the near future, including biomarker-driven treatments and immunotherapies. We presume that the clinical translation of these research efforts will improve the survival outcomes of this challenging disease, which are currently dismal.

Keywords: Pancreatic ductal adenocarcinoma; Molecular subtypes; Transcriptomic; Microenvironment; Precision medicine; Therapeutic targets; Immunotherapy

Core Tip: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death globally and is projected to be the second leading cause later. Kirsten rat sarcoma oncogene is a critical target for treatment regime evaluation in pancreatic ductal adenocarcinoma and proof of principle approaches have validated targeting in Kirsten rat sarcoma oncogene G12C. FOLFIRINOX and nab-paclitaxel gemcitabine are gold standard therapeutic in patients. The combinations were shown a survival benefit over previously standard gemcitabine monotherapy. Therapies targeting as well as immuno-therapies hold promise for the future but are currently not standard of care.