Publication Name	World Journal of Gastrointestinal Oncology
Manuscript ID	109923
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Minireviews
Article Title	Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors
Manuscript Source	Invited Manuscript
All Author List	Hui Nian, Yu Bai, Hong-Yang Wang, Hua Yu, Zhi-Long Zhang, Ru-Hong Shi, Shu Zhang, Yi-Bin Wu, De-Hua Zhou and Qian-Cheng Du
Funding Agency and Grant Number	Funding Agency Grant Number Hongkou District Health Commission of Shanghai Municipality "Hongwei" 2303-10
Corresponding Author	Qian-Cheng Du, MD, Department of Thoracic Surgery, Shanghai Xuhui Central Hospital, No. 366 Longchuan North Road, Xuhui District, Shanghai 200031, China. duqc1991106@sina.com
Key Words	Osteopontin; Gastrointestinal cancers; Chemoresistance; Targeted therapy; Tumor microenvironment remodeling
Core Tip	Osteopontin (OPN) drives gastrointestinal tumor progression by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway, promoting proliferation, metastasis, chemoresistance, and immune evasion. Key mechanisms involve upregulating anti-apoptotic proteins (e.g., B-cell lymphoma 2), inducing epithelial-mesenchymal transition via Snail/Twist, and remodeling the tumor microenvironment through VEGF-driven angiogenesis and cluster of differentiation 44-mediated immune suppression. Targeting this axis with PI3K/AKT inhibitors (e.g., Alpelisib) or OPN-neutralizing antibodies may reverse drug resistance and suppress metastasis. Challenges include pathway redundancy and the need for biomarker-guided precision strategies. Future research should focus on OPN isoform specificity, combination therapies (e.g., with immune checkpoint inhibitors), and multi-omics approaches to optimize outcomes in refractory cancers.
Citation	Nian H, Bai Y, Wang HY, Yu H, Zhang ZL, Shi RH, Zhang S, Wu YB, Zhou DH, Du QC. Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors. World J Gastrointest Oncol 2025; In press

Received	2025-05-27 02:03
Peer-Review Started	2025-05-27 02:03
To Make the First Decision
Return for Revision	2025-06-06 03:30
Revised	2025-06-14 09:12
Second Decision	2025-09-24 02:41
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-09-24 08:35
Articles in Press	2025-09-24 08:35
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-5204 (online)
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/
Copyright	© The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Permissions	For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
Publisher	Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Website	http://www.wjgnet.com