ArticleOncotarget2014
Efficacy of dual PI-3K and mTOR inhibitors in vitro and in vivo in acute lymphoblastic leukemia.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects.International journal of molecular sciences · 2022Review
- Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol.Frontiers in oncology · 2021Review
- Dual Kinase Targeting in Leukemia.Cancers · 2021Review
- 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
- Human BCR/ABL1 induces chronic myeloid leukemia-like disease in zebrafish.Haematologica · 2020Article
- Targeting mTOR in Acute Lymphoblastic Leukemia.Cells · 2019Review
- Dual PI3K/mTOR inhibitor BEZ235 as a promising therapeutic strategy against paclitaxel-resistant gastric cancer via targeting PI3K/Akt/mTOR pathway.Cell death & disease · 2018Article
- Cell-Penetrating CaCO₃ Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma.Cancers · 2018Article
- GZD824 suppresses the growth of human B cell precursor acute lymphoblastic leukemia cells by inhibiting the SRC kinase and PI3K/AKT pathways.Oncotarget · 2017Article
- The pan-BCL-2-blocker obatoclax (GX15-070) and the PI3-kinase/mTOR-inhibitor BEZ235 produce cooperative growth-inhibitory effects in ALL cells.Oncotarget · 2017Article
- The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia.Acta pharmacologica Sinica · 2017Article
- Article
- Regulation of the bone marrow microenvironment by G-CSF: Effects of G-CSF on acute lymphoblastic leukaemia.PloS one · 2017Article
- Article
- Targeting of PI3K/AKT/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development.Journal of hematology & oncology · 2016Article
- Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models.BMC cancer · 2016Article
- Low dose of lenalidmide and PI3K/mTOR inhibitor trigger synergistic cytoxicity in activated B cell-like subtype of diffuse large B cell lymphoma.Journal of experimental & clinical cancer research : CR · 2016Article
- Article
- Stromal cell-mediated mitochondrial redox adaptation regulates drug resistance in childhood acute lymphoblastic leukemia.Oncotarget · 2015Article
- Effect of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against human Merkel cell carcinoma MKL-1 cells.Oncology letters · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The major regulators of human acute lymphoblastic leukemia (ALL) cell growth and survival mediate their effects through the phosphoinositide 3-kinase (PI-3K)/mammalian target of rapamycin (mTOR) pathway. We have shown that the mTOR inhibitor everolimus extended survival in a non-obese diabetic/severe combined immune-deficient (NOD/SCID) mouse xenograft model of human ALL. Since PI-3K has mTOR dependent and independent functions we examined the effect of the dual PI-3K/mTOR inhibitors BEZ235 and BGT226. These agents inhibited the proliferation of ALL cell lines with a three log greater potency than everolimus. However, the induction of cell death differed, with BGT226 being cytotoxic in the low micromolar range while a two log higher concentration of BEZ235 was required to produce the same effect. While all three agents extended the survival of NOD/SCID mice engrafted with human ALL, the responses of individual xenografts varied. Although differential phosphorylation of AKT on Ser(473) and Thr(308) in response to everolimus exposure was observed, this did not entirely explain the different in vivo responses to the drugs. Our data suggests that while dual PI-3K/mTOR inhibitors may improve therapeutic outcomes for a subset of ALL patients, patient selection will be important, with some patients likely to respond better to single mTOR inhibition.
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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.