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

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

Table 4 Key mechanisms and interventions in targeted therapy of the Osteopontin-phosphatidylinositol 3-kinase/protein kinase B axis

Category	Key mechanisms	Intervention strategies	Related cancers
Small-molecule inhibitors	OPN activates PI3K/AKT to drive metastasis; PIK3CA mutations enhance pathway dependency	PI3Kα inhibitors (Alpelisib) combined with OPN-neutralizing antibodies	Pancreatic cancer, GC
Biomarker development	PIK3CA mutations (E542K/E545K) and OPN overexpression indicate PI3K activation; OPN regulates autophagy and immune microenvironment (IL-6/IL-8)	Alpelisib guided by PIK3CA mutation subtypes; Targeting OPN-immune interactions	GC, pancreatic cancer

OPN: Osteopontin; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; PIK3CA: Phosphatidylinositol-4:5-bisphosphate 3-kinase catalytic subunit alpha; E542K/E545K: Glutamic acid 542 to lysine/glutamic acid 545 to lysine; IL-6: Interleukin-6; IL-8: Interleukin-8; PI3Kα: Phosphatidylinositol 3-kinase catalytic subunit alpha; GC: Gastric Cancer.

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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]

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