ArticleCancer biology & therapy2018
PI3K/AKT/mTOR pathway inhibitors inhibit the growth of melanoma cells with mTOR H2189Y mutations in vitro.
Article in Cancer biology & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Metabolic reprogramming-a breakthrough point in overcoming resistance to BRAF mutant melanoma targeted therapy (Review).Oncology letters · 2026Review
- Hypomethylation-associated Sox11 upregulation promotes oncogenesis via the PI3K/AKT pathway in OLP-associated OSCC.Journal of cellular and molecular medicine · 2024Article
- Elucidating the Role of Lipid-Metabolism-Related Signal Transduction and Inhibitors in Skin Cancer.Metabolites · 2024Review
- Review
- Multidisciplinary approach and treatment of acral and mucosal melanoma.Frontiers in oncology · 2024Review
- Management of acral lentiginous melanoma: current updates and future directions.Frontiers in oncology · 2024Review
- Oncogenic DNA methyltransferase 1 activates the PI3K/AKT/mTOR signalling by blocking the binding of HSPB8 and BAG3 in melanoma.Epigenetics · 2023Article
- Synthesis, characterization, anticancer efficacy evaluation of ruthenium(II) and iridium(III) polypyridyl complexes toward A549 cells.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- Advanced Acral Melanoma Therapies: Current Status and Future Directions.Current treatment options in oncology · 2022Review
- Management of Acral and Mucosal Melanoma: Medical Oncology Perspective.The oncologist · 2022Review
- Synergistic effects of Rapamycin and Fluorouracil to treat a gastric tumor in a PTEN conditional deletion mouse model.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- Immunotherapy in Acral and Mucosal Melanoma: Current Status and Future Directions.Frontiers in immunology · 2021Review
- The tumor genetics of acral melanoma: What should a dermatologist know?JAAD international · 2020Article
- A20 promotes melanoma progression via the activation of Akt pathway.Cell death & disease · 2020Article
- Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway.Experimental and therapeutic medicine · 2020Article
- Article
- Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.Frontiers in molecular biosciences · 2020Review
- Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation.Nature communications · 2019Article
- UNBS5162 and amonafide inhibits tumor progression in human melanoma by the AKT/mTOR pathway.Cancer management and research · 2019Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mTOR is an important therapeutic target in many types of cancers. In melanoma, the mTOR nonsynonymous mutation rate is up to 10.4%. However, mTOR inhibitors have shown limited effects in clinical trials of melanoma. Because mTOR mutations are distributed, not selecting patients with specific mTOR mutations may be the main reason for therapeutic failures. Our previous research found that mutations in the mTOR P2213S and S2215Y kinase domains resulted in gain-of-function and were sensitive to specific inhibitors. The purpose of this study was to test the effect of heterozygous/homozygous H2189Y mutations on downstream pathways and sensitivity to inhibitors. mTOR kinase activity was analyzed by western blot and a K-LISA™ mTOR activity kit. The sensitivity of melanoma cells to inhibitors was tested by a proliferation assay. The expression of downstream pathway proteins was also analyzed by western blot. The results showed that heterozygous/homozygous H2189Y mutations were gain-of-function. The heterozygous H2189Y mutation was sensitive to the AKT inhibitor, AZD5363, and the phosphoinositide 3-kinase inhibitor, LY294002. The homozygous H2189Y mutation was sensitive to the mTOR inhibitor, everolimus, and the AKT inhibitors AZD5363 and MK-2206 2HCL,and the phosphoinositide 3-kinase inhibitor, LY294002. These results indicated that homozygous mutations in the kinase domain have a greater effect on protein function than heterozygous mutations. The mTOR kinase domain may play an important role in mTOR kinase activity and may be the target of selective inhibitors. Our study can facilitate the selection of appropriate inhibitors for patients in clinical trials.
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