Reference - Detail
| RRC ID | 78647 |
|---|---|
| Author | Sato T, Saito M, Nakajima S, Saito K, Katagata M, Fukai S, Okayama H, Sakamoto W, Saze Z, Momma T, Mimura K, Kono K. |
| Title | ARID1A deficiency is targetable by AKT inhibitors in HER2-negative gastric cancer. |
| Journal | Gastric Cancer |
| Abstract |
BACKGROUND:The PI3K/AKT signaling pathway is frequently activated in gastric cancer (GC); however, AKT inhibitors are not effective in unselected GC patients in clinical trials. Mutations in AT-rich interactive domain 1A (ARID1A), which are found in approximately 30% of GC patients, activate PI3K/AKT signaling, suggesting that targeting the ARID1A deficiency-activated PI3K/AKT pathway is a therapeutic candidate for ARID1A-deficient GC. METHODS:The effect of AKT inhibitors was evaluated using cell viability and colony formation assays in ARID1A-deficient and ARID1A knockdown ARID1A-WT GC cells as well as in HER2-positive and HER2-negative GC. The Cancer Genome Atlas cBioPortal and Gene Expression Omnibus microarray databases were accessed to determine the extent of dependence of GC cell growth on the PI3K/AKT signaling pathway. RESULTS:AKT inhibitors decreased the viability of ARID1A-deficient cells and the inhibitory effect was greater in ARID1A-deficient/HER2-negative GC cells. Bioinformatics data suggested that PI3K/AKT signaling plays a greater role in proliferation and survival in ARID1A-deficient/HER2-negative GC cells than in ARID1A-deficient/HER2-positive cells, supporting the higher therapeutic efficacy of AKT inhibitors. CONCLUSIONS:The effect of AKT inhibitors on cell proliferation and survival is affected by HER2 status, providing a rationale for exploring targeted therapy using AKT inhibitors in ARID1A-deficient/HER2-negative GC. |
| Volume | 26(3) |
| Pages | 379-392 |
| Published | 2023-5-1 |
| DOI | 10.1007/s10120-023-01373-6 |
| PII | 10.1007/s10120-023-01373-6 |
| PMID | 36811690 |
| MeSH | Cell Line, Tumor DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Humans Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-akt / metabolism Signal Transduction Stomach Neoplasms* / drug therapy Stomach Neoplasms* / genetics Stomach Neoplasms* / metabolism Transcription Factors* / metabolism |
| Resource | |
| Human and Animal Cells | NUGC-4(RCB1939) MKN7(RCB0999) MKN45(RCB1001) |