Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors

doi:10.4251/wjgo.v17.i11.109923

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 17, Issue 11

This Article

(48)

(60)

(0)

(11)

(2)

(747)

(1)

Peer-Review Report of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Journal Information of This Article

Publication Name

World Journal of Gastrointestinal Oncology

ISSN

1948-5204

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Minireviews

World J Gastrointest Oncol. Nov 15, 2025; 17(11): 109923
Published online Nov 15, 2025. doi: 10.4251/wjgo.v17.i11.109923

Table 3 Osteopontin-mediated therapeutic resistance mechanisms and interventions

Mechanism category	Key molecules/pathways	Functional effects	Intervention strategies	Related cancers
Chemoresistance	PI3K/AKT/mTOR, NEMO-ATM/IKKα, DNA repair pathways	Enhances DNA damage repair; Reduces sensitivity to 5-FU/radiotherapy	Wortmannin (PI3K inhibitor), PRDM15 knockout	Colorectal cancer
Targeted therapy resistance	HER2/EGFR, PI3K/AKT-EMT, DTL	Inhibits trastuzumab efficacy; Activates EMT; Upregulates pro-survival genes (e.g., Bcl-2)	OPN-neutralizing antibodies, LY294002	GC, HCC, pancreatic cancer
Autophagy-mediated resistance	OPN/NF-κB, DRP1, LC3-II/p62	Sustains chemoresistance via autophagic flux blockade	Liensinine (autophagy inhibitor), DRP1 activation	Lung adenocarcinoma
Immune evasion	CD44-PI3K/AKT, VEGF/IL-8	Reprograms TME to suppress CD8+ T cell infiltration	αRANKL blockade, Anti-VEGF/IL-8 antibodies	NSCLC, bone metastatic cancers

OPN: Osteopontin; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; mTOR: Mechanistic target of rapamycin; NEMO: NF-κB essential modulator; ATM: Ataxia-telangiectasia mutated; IKKα: IκB kinase alpha; HER2: Human epidermal growth factor receptor 2; EGFR: Epidermal growth factor receptor; EMT: Epithelial-mesenchymal transition; Bcl-2: B-cell lymphoma 2; DTL: Denticleless e3 ubiquitin protein ligase homolog; NF-κB: Nuclear Factor kappa-light-chain-enhancer of activated B Cells; DRP1: Dynamin-related protein 1; LC3-II: Microtubule-associated protein 1A/1B-light chain 3-II; p62: Sequestosome 1; CD44: Cluster of differentiation 44; VEGF: Vascular endothelial growth factor; IL-8: Interleukin-8; PRDM15: PR/SET Domain 15; LY294002: PI3K inhibitors; αRANKL: Anti-receptor activator of nuclear factor kappa-B ligand antibody; VEGF: Vascular endothelial growth factor; GC: Gastric cancer; HCC: Hepatocellular carcinoma; NSCLC: Non-small cell lung cancer.

Full Size Table

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; 17(11): 109923
URL: https://www.wjgnet.com/1948-5204/full/v17/i11/109923.htm
DOI: https://dx.doi.org/10.4251/wjgo.v17.i11.109923

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; 17(11): 109923 [PMID: 41281471 DOI: 10.4251/wjgo.v17.i11.109923]

All content on this site: Copyright © 1993-2026 Baishideng Publishing Group Inc, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies. For all open access content, the relevant licensing terms apply.