ArticlePloS one2012
Utility of a PI3K/mTOR inhibitor (NVP-BEZ235) for thyroid cancer therapy.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- MEN 2A-related cutaneous lichen amyloidosis: report of three kindred and systematic literature review of clinical, biochemical and molecular characteristics.Familial cancer · 2016Pooled it
- Cancer Stemness and Dedifferentiation in Anaplastic Thyroid Carcinoma: Insights into a Multigenic, Microenvironmental Network and the Role of CD44.Biomedicines · 2026Review
- Targeting Ataxia Telangiectasia-Mutated and Rad3-Related for Anaplastic Thyroid Cancer.Cancers · 2025Article
- Developments in the study of the role of lactate metabolism in the genesis and progression of thyroid cancer.Frontiers in cell and developmental biology · 2025Review
- Obesity-Associated Colorectal Cancer.International journal of molecular sciences · 2024Review
- YTHDC2 Retards Cell Proliferation and Triggers Apoptosis in Papillary Thyroid Cancer by Regulating CYLD-Mediated Inactivation of Akt Signaling.Applied biochemistry and biotechnology · 2024Article
- Clinical Implications of mTOR Expression in Papillary Thyroid Cancer-A Systematic Review.Cancers · 2023Review
- Down-Regulation of the Mammalian Target of Rapamycin (mTOR) Pathway Mediates the Effects of the Paeonol-Platinum(II) Complex in Human Thyroid Carcinoma Cells and Mouse SW1736 Tumor Xenografts.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- A dual PI3 kinase/mTOR inhibitor BEZ235 reverses doxorubicin resistance in ABCB1 overexpressing ovarian and pancreatic cancer cell lines.Biochimica et biophysica acta. General subjects · 2020Article
- Apoptosis Activation in Thyroid Cancer Cells by Jatrorrhizine-Platinum(II) Complex via Downregulation of PI3K/AKT/Mammalian Target of Rapamycin (mTOR) Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- The PI3K pathway impacts stem gene expression in a set of glioblastoma cell lines.Journal of cancer research and clinical oncology · 2020Article
- NVP-BEZ235 inhibits thyroid cancer growth by p53- dependent/independent p21 upregulation.International journal of biological sciences · 2020Article
- Synergy of GSK-J4 With Doxorubicin in KRAS-Mutant Anaplastic Thyroid Cancer.Frontiers in pharmacology · 2020Article
- Genetic alterations in anaplastic thyroid carcinoma and targeted therapies.Experimental and therapeutic medicine · 2019Review
- Poorly Differentiated Carcinoma of the Thyroid Gland: Current Status and Future Prospects.Thyroid : official journal of the American Thyroid Association · 2019Review
- Lyn Kinase Promotes the Proliferation of Malignant Melanoma Cells through Inhibition of Apoptosis and Autophagy via the PI3K/Akt Signaling Pathway.Journal of Cancer · 2019Article
- Therapeutic effects of adenovirus-mediated CD and NIS expression combined with NaOncology letters · 2017Article
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- A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer.PloS one · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe assessed the utility of the dual PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235) as single agent therapy and in combination with conventional chemotherapy for thyroid cancer. METHODOLOGY/PRINCIPAL
findingsEight cell lines from four types of thyroid cancer (papillary, follicular, anaplastic, medullary) were studied. The cytotoxicity of BEZ235 and five conventional chemotherapeutic agents alone and in combination was measured using LDH assay. Quantitative western blot assessed expression of proteins associated with cell cycle, apoptosis and signaling pathways. Cell cycle distribution and apoptosis were measured by flow cytometry. Murine flank anaplastic thyroid cancers (ATC) were treated with oral BEZ235 daily. We found that BEZ235 effectively inhibited cell proliferation of all cancer lines, with ATC exhibiting the greatest sensitivity. BEZ235 consistently inactivated signaling downstream of mTORC1. BEZ235 generally induced cell cycle arrest at G0/G1 phase, and also caused apoptosis in the most sensitive cell lines. Baseline levels of p-S6 ribosomal protein (Ser235/236) and p27 correlated with BEZ235 sensitivity. Growth of 8505C ATC xenograft tumors was inhibited with BEZ235, without any observed toxicity. Combination therapy of BEZ235 and paclitaxel consistently demonstrated synergistic effects against ATC in vitro.
conclusionsBEZ235 as a single therapeutic agent inhibits thyroid cancer proliferation and has synergistic effects in combination with paclitaxel in treating ATC. These findings encourage future clinical trials using BEZ235 for patients with this fatal disease.
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