ArticlePloS one2013
Differential effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway in acute lymphoblastic leukemia.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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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
35 citing papers in PubMed, 70 citations in OpenAlex.
- Emerging Therapeutic Targets and Drug Resistance Mechanisms in Immunotherapy of Hematological Malignancies.Cancers · 2023Review
- SIRT2 inhibitor SirReal2 enhances anti-tumor effects of PI3K/mTOR inhibitor VS-5584 on acute myeloid leukemia cells.Cancer medicine · 2023Article
- Activation of signaling pathways in models of t(6;9)-acute myeloid leukemia.Annals of hematology · 2022Article
- Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11.Journal of nanobiotechnology · 2022Article
- Molecular docking analysis of mTOR protein kinase with chromatographically characterized compounds fromBioinformation · 2022Article
- Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1Annals of hematology · 2021Article
- Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol.Frontiers in oncology · 2021Review
- A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia.BMC pharmacology & toxicology · 2020Article
- Targeting mTOR in Acute Lymphoblastic Leukemia.Cells · 2019Review
- MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: the mechanism of synergic killing of human T-ALL cells.Acta pharmacologica Sinica · 2018Article
- Non ABL-directed inhibitors as alternative treatment strategies for chronic myeloid leukemia.Molecular cancer · 2018Review
- Pantoprazole Induces Apoptosis of Leukemic Cells by Inhibiting Expression of P-Glycoprotein/Multidrug Resistance-Associated Protein-1 Through PI3K/AKT/mTOR Signaling.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2017Article
- Control of B lymphocyte development and functions by the mTOR signaling pathways.Cytokine & growth factor reviews · 2017Review
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- New Insights into mTOR Signal Pathways in Ovarian-Related Diseases: Polycystic Ovary Syndrome and Ovarian CancerAsian Pacific journal of cancer prevention : APJCP · 2016Article
- Targeting of PI3K/AKT/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development.Journal of hematology & oncology · 2016Article
- Upregulation of miR-181c inhibits chemoresistance by targeting ST8SIA4 in chronic myelocytic leukemia.Oncotarget · 2016Article
- The pyrrolo-1,5-benzoxazepine, PBOX-15, enhances TRAIL‑induced apoptosis by upregulation of DR5 and downregulation of core cell survival proteins in acute lymphoblastic leukaemia cells.International journal of oncology · 2016Article
- Intracellular Signaling Pathways Involved in Childhood Acute Lymphoblastic Leukemia; Molecular Targets.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2016Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAberrant PI3K/AKT/mTOR signaling has been linked to oncogenesis and therapy resistance in various malignancies including leukemias. In Philadelphia chromosome (Ph) positive leukemias, activation of PI3K by dysregulated BCR-ABL tyrosine kinase (TK) contributes to the pathogenesis and development of resistance to ABL-TK inhibitors (TKI). The PI3K pathway thus is an attractive therapeutic target in BCR-ABL positive leukemias, but its role in BCR-ABL negative ALL is conjectural. Moreover, the functional contribution of individual components of the PI3K pathway in ALL has not been established. EXPERIMENTAL
designWe compared the activity of the ATP-competitive pan-PI3K inhibitor NVP-BKM120, the allosteric mTORC1 inhibitor RAD001, the ATP-competitive dual PI3K/mTORC1/C2 inhibitors NVP-BEZ235 and NVP-BGT226 and the combined mTORC1 and mTORC2 inhibitors Torin 1, PP242 and KU-0063794 using long-term cultures of ALL cells (ALL-LTC) from patients with B-precursor ALL that expressed the BCR-ABL or TEL-ABL oncoproteins or were BCR-ABL negative.
resultsDual PI3K/mTOR inhibitors profoundly inhibited growth and survival of ALL cells irrespective of their genetic subtype and their responsiveness to ABL-TKI. Combined suppression of PI3K, mTORC1 and mTORC2 displayed greater antileukemic activity than selective inhibitors of PI3K, mTORC1 or mTORC1 and mTORC2.
conclusionsInhibition of the PI3K/mTOR pathway is a promising therapeutic approach in patients with ALL. Greater antileukemic activity of dual PI3K/mTORC1/C2 inhibitors appears to be due to the redundant function of PI3K and mTOR. Clinical trials examining dual PI3K/mTORC1/C2 inhibitors in patients with B-precursor ALL are warranted, and should not be restricted to particular genetic subtypes.
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