ArticleInternational journal of molecular sciences2020
Synergistic Effects of Combination Therapy with AKT and mTOR Inhibitors on Bladder Cancer Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Overcoming mTOR Inhibitor Resistance: From Biological Basis to Therapeutic Strategies.Biomedicines · 2026Review
- MFSynDCP: multi-source feature collaborative interactive learning for drug combination synergy prediction.BMC bioinformatics · 2024Article
- Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer-An Exploratory Analysis of Clinical and Tumor Biological Significance.International journal of molecular sciences · 2024Article
- Landscape of targeted therapies for advanced urothelial carcinoma.Exploration of targeted anti-tumor therapy · 2024Review
- Reflections on the Biology of Cell Culture Models: Living on the Edge of Oxidative Metabolism in Cancer Cells.International journal of molecular sciences · 2023Review
- Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.Frontiers in pharmacology · 2023Review
- Emerging Roles for Mammalian Target of Rapamycin (mTOR) Complexes in Bladder Cancer Progression and Therapy.Cancers · 2022Review
- Evaluation of synergism in drug combinations and reference models for future orientations in oncology.Current research in pharmacology and drug discovery · 2022Review
- mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?Frontiers of medicine · 2021Review
- Oncoimmunology Meets Organs-on-Chip.Frontiers in molecular biosciences · 2021Review
- An Overview of Methods and Tools for Transfection of Eukaryotic CellsFrontiers in bioengineering and biotechnology · 2021Review
- SPR965, a Dual PI3K/mTOR Inhibitor, as a Targeted Therapy in Ovarian Cancer.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Despite comprehensive genomic analyses, no targeted therapies are approved for bladder cancer. Here, we investigate whether a single and combination therapy with targeted agents exert antitumor effects on bladder cancer cells through genomic alterations using a three-dimensional (3D) high-throughput screening (HTS) platform. Seven human bladder cancer cell lines were used to screen 24 targeted agents. The effects of 24 targeted agents were dramatically different according to the genomic alterations of bladder cancer cells. BEZ235 (dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor) showed antitumor effects against most cell lines, while AZD2014 (mTOR inhibitor) had an IC50 value lower than 2 μM in 5637, J82, and RT4 cell lines. AZD5363 (protein kinase B (AKT) inhibitor) exerted antitumor effects on 5637, J82, and 253J-BV cells. J82 cells (PI3KCA and mTOR mutations) were sensitive to AZD5363, AZD2014, and BEZ235 alone or in AZD5363/AZD2014 and AZD5363/BEZ235 combinations. Although all single drugs suppressed cell proliferation, the combination of drugs exhibited synergistic effects on cell viability and colony formation. The synergistic effects of the combination therapy on the PI3K/Akt/mTOR pathway, apoptosis, and EMT were evident in Western blotting. Thus, the 3D culture-based HTS platform could serve as a useful preclinical tool to evaluate various drug combinations.
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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.