ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
PTEN loss does not predict for response to RAD001 (Everolimus) in a glioblastoma orthotopic xenograft test panel.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K.Neuro-oncology · 2015Trial
- Predicting everolimus treatment efficacy in patients with advanced endometrial carcinoma: a GINECO group study.Targeted oncology · 2013Trial
- Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma.Journal of neuro-oncology · 2010Trial
- Real-time evaluation of glioblastoma growth in patient-specific zebrafish xenografts.Neuro-oncology · 2022Article
- Targeting mutations in cancer.The Journal of clinical investigation · 2022Review
- Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models.Frontiers in oncology · 2022Article
- OncoKB: A Precision Oncology Knowledge Base.JCO precision oncology · 2017Article
- Network Modeling Identifies Patient-specific Pathways in Glioblastoma.Scientific reports · 2016Article
- InsR/IGF1R Pathway Mediates Resistance to EGFR Inhibitors in Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Genetic biomarkers of drug response for small-molecule therapeutics targeting the RTK/Ras/PI3K, p53 or Rb pathway in glioblastoma.CNS oncology · 2016Review
- STAT3 Serine 727 Phosphorylation: A Relevant Target to Radiosensitize Human Glioblastoma.Brain pathology (Zurich, Switzerland) · 2016Article
- Src family kinases differentially influence glioma growth and motility.Molecular oncology · 2015Article
- Toward rapamycin analog (rapalog)-based precision cancer therapy.Acta pharmacologica Sinica · 2015Review
- Visualizing cancer and response to therapy in vivo using Cy5.5-labeled factor VIIa and anti-tissue factor antibody.Journal of drug targeting · 2015Article
- The challenges and the promise of molecular targeted therapy in malignant gliomas.Neoplasia (New York, N.Y.) · 2015Review
- Combined PTEN Mutation and Protein Expression Associate with Overall and Disease-Free Survival of Glioblastoma Patients.Translational oncology · 2014Article
- Molecular alterations of PI3K/Akt/mTOR pathway: a therapeutic target in endometrial cancer.TheScientificWorldJournal · 2014Review
- The evolution of the TOR pathway and its role in cancer.Oncogene · 2013Review
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeHyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus). EXPERIMENTAL
designTo test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN.
resultsConsistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas 1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy.
conclusionThese data suggest that loss of PTEN function is insufficient to adequately predict responsiveness to mTOR inhibitors in glioblastoma multiforme.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.