ArticleBritish journal of cancer2013
PTEN deficiency is associated with reduced sensitivity to mTOR inhibitor in human bladder cancer through the unhampered feedback loop driving PI3K/Akt activation.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
- A phase 2 trial of buparlisib in patients with platinum-resistant metastatic urothelial carcinoma.Cancer · 2020Trial
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- Glyoxalase 2 Drives D-Lactate Oncometabolite Signaling to Promote Prostate Cancer Aggressiveness via FAK/Src Activation.Antioxidants (Basel, Switzerland) · 2026Article
- Tumor suppressor network dysregulation in neuroblastoma: molecular mechanisms and precision therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Anticancer effects of salvianolic acid A through multiple signaling pathways (Review).Molecular medicine reports · 2025Review
- Repurposing Amiodarone for Bladder Cancer Treatment.Cancer research communications · 2025Article
- Lysine Methyltransferase 9 (KMT9) Is an Actionable Target in Muscle-Invasive Bladder Cancer.Cancers · 2024Article
- Targeting CD24 as a novel immunotherapy for solid cancers.Cell communication and signaling : CCS · 2023Review
- Genomics and Immunomics in the Treatment of Urothelial Carcinoma.Current oncology (Toronto, Ont.) · 2022Review
- Review
- Downregulated exosomal microRNA-148b-3p in cancer associated fibroblasts enhance chemosensitivity of bladder cancer cells by downregulating the Wnt/β-catenin pathway and upregulating PTEN.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- The biochemical and clinical implications of phosphatase and tensin homolog deleted on chromosome ten in different cancers.American journal of cancer research · 2021Review
- PTEN suppresses epithelial-mesenchymal transition and cancer stem cell activity by downregulating Abi1.Scientific reports · 2020Article
- Identification of key pathways and genes in PTEN mutation prostate cancer by bioinformatics analysis.BMC medical genetics · 2019Article
- Everolimus inhibits the proliferation and migration of epidermal growth factor receptor-resistant lung cancer cells A549 via regulating the microRNA-4328/phosphatase and tensin homolog signaling pathway.Oncology letters · 2019Article
- Sulfated polysaccharide ofAging · 2019Article
- Botulinum toxin type A prevents the phenotypic transformation of fibroblasts induced by TGF‑β1 via the PTEN/PI3K/Akt signaling pathway.International journal of molecular medicine · 2019Article
- MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: the mechanism of synergic killing of human T-ALL cells.Acta pharmacologica Sinica · 2018Article
- Pilot study of sirolimus in patients with PIK3CA mutant/amplified refractory solid cancer.Molecular and clinical oncology · 2017Article
- Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas.Pathology research international · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPreclinical studies have shown that PTEN loss enhances sensitivity to mammalian target of Rapamycin (mTOR) inhibitors because of facilitated PI3K (phosphatidylinositol-3 kinase)/Akt activation and consecutive stimulation of the mTOR pathway. In patients with advanced transitional cell carcinoma (TCC) treated with the mTOR inhibitor everolimus, PTEN loss was, however, associated with resistance to treatment.
methodsTransitional cell carcinoma specimens, human bladder cancer cells and derived mouse xenografts were used to evaluate how the PTEN status influences the activity of mTOR inhibitors.
resultsTransitional cell carcinoma patients with a shorter progression-free survival under everolimus exhibited PTEN deficiency and increased Akt activation. Moreover, PTEN-deficient bladder cancer cells were less sensitive to rapamycin than cells expressing wild-type PTEN, and rapamycin strikingly induced Akt activation in the absence of functional PTEN. Inhibition of Akt activation by the PI3K inhibitor wortmannin interrupted this rapamycin-induced feedback loop, thereby enhancing the antiproliferative effects of the mTOR inhibitor both in vitro and in vivo.
conclusionFacilitation of Akt activation upon PTEN loss can have a more prominent role in driving the feedback loop in response to mTOR inhibition than in promoting the mTOR pathway. These data support the use of both PI3K and mTOR inhibitors to treat urothelial carcinoma, in particular in the absence of functional PTEN.
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