ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Phosphatidylinositol-3-kinase as a therapeutic target in melanoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 71 citations in OpenAlex.
- Mechanistic Insights into Glycine's Regulation of Milk Protein Synthesis via PI3K-AKT-mTOR Signaling.Current issues in molecular biology · 2026Article
- Decoding the Role of Lipid Metabolism and Membrane Dynamics in Melanoma.International journal of molecular sciences · 2026Review
- Article
- Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Predicting Genomic Alterations of Phosphatidylinositol-3 Kinase Signaling in Hepatocellular Carcinoma: A Radiogenomics Study Based on Next-Generation Sequencing and Contrast-Enhanced CT.Annals of surgical oncology · 2022Article
- Mechanical and metabolic interplay in the brain metastatic microenvironment.Frontiers in oncology · 2022Article
- Zearalenone promotes apoptosis of mouse Leydig cells by targeting phosphatase and tensin homolog and thus inhibiting the PI3K/AKT signal pathway.Environmental science and pollution research international · 2021Article
- Histone Deacetylase Inhibitors as Multitarget-Directed Epi-Drugs in Blocking PI3K Oncogenic Signaling: A Polypharmacology Approach.International journal of molecular sciences · 2020Review
- Emerging roles of class I PI3K inhibitors in modulating tumor microenvironment and immunity.Acta pharmacologica Sinica · 2020Review
- Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives.Cancers · 2020Review
- Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma.Cell death & disease · 2020Article
- Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence.Signal transduction and targeted therapy · 2020Review
- Parthenolide Augments the Chemosensitivity of Non-small-Cell Lung Cancer to CisplatinFrontiers in cell and developmental biology · 2020Article
- Metabolic and lipidomic investigation of the antiproliferative effects of coronatine against human melanoma cells.Scientific reports · 2019Article
- Targeting PI3K in cancer: mechanisms and advances in clinical trials.Molecular cancer · 2019Review
- Salidroside inhibits steroid-induced avascular necrosis of the femoral head via the PI3K/Akt signaling pathway: In vitro and in vivo studies.Molecular medicine reports · 2018Article
- Treatment of melanoma with selected inhibitors of signaling kinases effectively reduces proliferation and induces expression of cell cycle inhibitors.Medical oncology (Northwood, London, England) · 2017Article
- Discovery of potential biomarkers in human melanoma cells with different metastatic potential by metabolic and lipidomic profiling.Scientific reports · 2017Article
- A caveolin-dependent and PI3K/AKT-independent role of PTEN in β-catenin transcriptional activity.Nature communications · 2015Article
- p85 protein expression is associated with poor survival in HER2-positive patients with advanced breast cancer treated with trastuzumab.Pathology oncology research : POR · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
purposePhosphatidylinositol-3 kinases (PI3K) are critical for malignant cellular processes including growth, proliferation, and survival, and are targets of drugs in clinical development. We assessed expression of PI3K in melanomas and nevi, and studied associations between PI3K pathway members and in vitro response to a PI3K inhibitor, LY294002. EXPERIMENTAL
designUsing Automated Quantitative Analysis, we quantified expression of p85 and p110alpha subunits in 540 nevi and 523 melanomas. We determined the IC(50) for LY294002 for 11 melanoma cell lines and, using reverse phase protein arrays, assessed the association between levels of PI3K pathway members and sensitivity to LY294002.
resultsp85 and p110alpha tend to be coexpressed (P < 0.0001); expression was higher in melanomas than nevi (P < 0.0001) for both subunits, and higher in metastatic than primary melanomas for p85 (P < 0.0001). Although phospho-Akt (pAkt) levels decreased in all cell lines treated with LY294002, sensitivity was variable. We found no association by t tests between baseline p85, p110alpha, and pAkt levels and sensitivity to LY294002, whereas pS6 Ser(235) and Ser(240) were lower in the more resistant cell lines (P = 0.01 and P = 0.004, respectively).
conclusionsExpression of p85 and p110alpha subunits is up-regulated in melanoma, indicating that PI3K is a good drug target. Pretreatment pS6 levels correlated with sensitivity to the PI3K inhibitor, LY294002, whereas PI3K and pAkt did not, suggesting that full activation of the PI3K pathway is needed for sensitivity to PI3K inhibition. pS6 should be evaluated as a predictor of response in melanoma patients treated with PI3K inhibitors, as these drugs enter clinical trials.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.