| 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. |
| Article Reprints |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/247
|
| 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 |
| 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. |
| Publish Date |
2025-11-14 00:56 |
| Citation |
<p>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. <i>World J Gastrointest Oncol</i> 2025; 17(11): 109923</p> |
| URL |
https://www.wjgnet.com/1948-5204/full/v17/i11/109923.htm |
| DOI |
https://dx.doi.org/10.4251/wjgo.v17.i11.109923 |
