ArticleJournal of translational medicine2011
Characterization and targeting of phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in renal cell cancer.
Article in Journal of translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Long non-coding RNAs in renal cell carcinoma: A systematic review and clinical implications.Oncotarget · 2017Pooled it
- Role of the circular RNAs/microRNA/messenger RNA axis in renal cell carcinoma: From gene regulation to metabolism and immunity.iScience · 2025Review
- Inhibition of PI3K-AKT-mTOR pathway and modulation of histone deacetylase enzymes reduce the growth of acute myeloid leukemia cells.Medical oncology (Northwood, London, England) · 2023Article
- Dual inhibition of atypical PKC signaling and PI3K/Akt signaling dysregulates c-Myc to induce apoptosis in clear cell Renal Cell Carcinoma.Frontiers in oncology · 2023Article
- CircRNAs as Novel Biomarkers and Therapeutic Targets in Renal Cell Carcinoma.Frontiers in molecular biosciences · 2022Review
- Recent Advances in Dual PI3K/mTOR Inhibitors for Tumour Treatment.Frontiers in pharmacology · 2022Review
- Circular RNAs and their role in renal cell carcinoma: a current perspective.Cancer cell international · 2021Review
- Exosomal circular RNA_400068 promotes the development of renal cell carcinoma via the miR‑210‑5p/SOCS1 axis.Molecular medicine reports · 2020Article
- Circular RNAs in renal cell carcinoma: implications for tumorigenesis, diagnosis, and therapy.Molecular cancer · 2020Review
- Curcumin Nanoparticle Enhances the Anticancer Effect of Cisplatin by Inhibiting PI3K/AKT and JAK/STAT3 Pathway in Rat Ovarian Carcinoma Induced by DMBA.Frontiers in pharmacology · 2020Article
- Development and Validation of Nine-RNA Binding Protein Signature Predicting Overall Survival for Kidney Renal Clear Cell Carcinoma.Frontiers in genetics · 2020Article
- lncRNA ROR promotes the progression of renal cell carcinoma through the miR‑206/VEGF axis.Molecular medicine reports · 2019Article
- [Pt(Biomolecules · 2019Article
- Preclinical evaluation of novel PI3K/mTOR dual inhibitor SN202 as potential anti-renal cancer agent.Cancer biology & therapy · 2018Article
- Therapeutic Use of mTOR Inhibitors in Renal Diseases: Advances, Drawbacks, and Challenges.Oxidative medicine and cellular longevity · 2018Review
- The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review.International journal of molecular sciences · 2017Review
- Novel drugs that target the metabolic reprogramming in renal cell cancer.Cancer & metabolism · 2016Review
- PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation and tumor development in renal distal tubules of rats and men.Oncotarget · 2015Article
- Novel mutations and role of the LKB1 gene as a tumor suppressor in renal cell carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Metabolic syndrome and renal cell carcinoma.World journal of surgical oncology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPI3K and mTOR are key components of signal transduction pathways critical for cell survival. Numerous PI3K inhibitors have entered clinical trials, while mTOR is the target of approved drugs for metastatic renal cell carcinoma (RCC). We characterized expression of p85 and p110α PI3K subunits and mTOR in RCC specimens and assessed pharmacologic co-targeting of these molecules in vitro.
methodsWe employed tissue microarrays containing 330 nephrectomy cases using a novel immunofluorescence-based method of Automated Quantitative Analysis (AQUA) of in situ protein expression. In RCC cell lines we assessed synergism between PI3K and mTOR inhibitors and activity of NVP-BEZ235, which co-targets PI3K and mTOR.
resultsp85 expression was associated with high stage and grade (P < 0.0001 for both). High p85 and high mTOR expression were strongly associated with decreased survival, and high p85 was independently prognostic on multi-variable analysis. Strong co-expression of both PI3K subunits and mTOR was found in the human specimens. The PI3K inhibitor LY294002 and rapamycin were highly synergistic in all six RCC cell lines studied. Similar synergism was seen with all rapamycin concentrations used. NVP-BEZ235 inhibited RCC cell growth in vitro with IC(50)s in the low ηM range and resultant PARP cleavage.
conclusionsHigh PI3K and mTOR expression in RCC defines populations with decreased survival, suggesting that they are good drug targets in RCC. These targets tend to be co-expressed, and co-targeting these molecules is synergistic. NVP-BEZ235 is active in RCC cells in vitro; suggesting that concurrent PI3K and mTOR targeting in RCC warrants further investigation.
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What Socratic 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 Socratic graph.