PI3K/AKT/mTOR Pathway Dynamics in Gastric Cancer
Summary
The PI3K/AKT/mTOR cascade is a central regulator of cell growth, metabolism and survival in gastric epithelial cells. Activation begins with PI3K‐mediated production of phosphatidylinositol-3,4,5-trisphosphate at the plasma membrane, leading to recruitment and activation of AKT by PDK1 and mTORC2 complexes. Activated AKT phosphorylates downstream effectors such as TSC2 and PRAS40, relieving inhibition of mTORC1. mTORC1 then controls protein synthesis and autophagy through S6 kinases and 4E-BP1. In gastric cancer, genetic alterations including PIK3CA amplification, PTEN loss or receptor tyrosine kinase over-expression drive constitutive pathway activation. Aberrant PI3K/AKT/mTOR signalling promotes tumour initiation, angiogenesis, lymphangiogenesis, metastatic spread and chemoresistance. Dynamic feedback loops between mTORC1 and IRS proteins, and extensive crosstalk with MAPK and immune networks, further complicate signal modulation. Therapeutic efforts have produced dual PI3K/mTOR inhibitors and selective mTORC1 blockers, often in combination with HER2-targeted or cytotoxic agents, underscoring the need for biomarker-guided strategies and deeper insight into pathway plasticity.
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PI3K/AKT/mTOR Pathway Dynamics in Gastric Cancer publication trend
The graph below shows the total number of articles in pi3k/akt/mtor pathway dynamics in gastric cancer across all publications each year (not limited to Nature Index journals).
Technical terms
Phosphorylation: Addition of a phosphate group to a protein or lipid, modulating its activity.
Ubiquitination: Attachment of ubiquitin to a protein, often marking it for proteasomal degradation.
mTORC1/mTORC2: Distinct mTOR protein complexes regulating cell growth (mTORC1) and survival (mTORC2).
Insulin receptor substrate (IRS): Adaptor proteins that transmit signals from activated receptors to downstream kinases.
Patient-derived xenograft: Tumour tissue transplanted into an immunodeficient mouse to model human cancer biology.
References
- PILRB potentiates the PI3K/AKT signaling pathway and reprograms cholesterol metabolism to drive gastric tumorigenesis and metastasis. Cell Death & Disease (2024).
- TMEM65 promotes gastric tumorigenesis by targeting YWHAZ to activate PI3K-Akt-mTOR pathway and is a therapeutic target. Oncogene (2024).
- Signaling pathways and therapeutic interventions in gastric cancer. Signal Transduction and Targeted Therapy (2022).
- The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma. Cancers (2014).
- Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer. BMC Cancer (2012).
- Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis. BMC Cancer (2015).
- Roles of PTEN (Phosphatase and Tensin Homolog) in Gastric Cancer Development and Progression. Asian Pacific Journal of Cancer Prevention (2014).
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