ArticleOncotarget2012
Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels.
Article in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 71 citations in OpenAlex.
- Preclinical and early clinical evaluation of the oral AKT inhibitor, MK-2206, for the treatment of acute myelogenous leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
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- The cross-talk between GSK-3β, RKIP, and PTEN as potential targets for therapeutic implications in cancer: a comprehensive insight.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- Article
- Inhibition of GRK2-PDE4D Axis Suppresses Fibroblast-Like Synoviocytes Hyperplasia and Alleviates Experimental Arthritis.International journal of biological sciences · 2025Article
- Glucocorticoid Therapy in Acute Lymphoblastic Leukemia: Navigating Short-Term and Long-Term Effects and Optimal Regimen Selection.Current hematologic malignancy reports · 2024Review
- Integrating rapamycin with novel PI3K/Akt/mTOR inhibitor microRNAs on NOTCH1-driven T-cell acute lymphoblastic leukemia (T-ALL).BioImpacts : BI · 2024Article
- WDR54 exerts oncogenic roles in T-cell acute lymphoblastic leukemia.Cancer science · 2023Article
- Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects.International journal of molecular sciences · 2022Review
- Dual Kinase Targeting in Leukemia.Cancers · 2021Review
- Hypomorphic mTOR Downregulates CDK6 and Delays Thymic Pre-T LBL Tumorigenesis.Molecular cancer therapeutics · 2020Article
- 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
- Repurposing Eukaryotic Kinase Inhibitors as Colistin Adjuvants in Gram-Negative Bacteria.ACS infectious diseases · 2019Article
- Positive Effects of PI3K/Akt Signaling Inhibition on PTEN and P53 in Prevention of Acute Lymphoblastic Leukemia Tumor Cells.Advanced pharmaceutical bulletin · 2019Article
- Article
- Expression of the miR-150 tumor suppressor is restored by and synergizes with rapamycin in a human leukemia T-cell line.Leukemia research · 2018Article
- Biological Aspects of mTOR in Leukemia.International journal of molecular sciences · 2018Review
- Article
- Polymorphism rs1385129 Within Glut1 GeneFrontiers in immunology · 2018Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignant hematological disorder arising in the thymus from T-cell progenitors. T-ALL mainly affects children and young adults, and remains fatal in 20% of adolescents and 50% of adults, despite progress in polychemotherapy protocols. Therefore, innovative targeted therapies are desperately needed for patients with a dismal prognosis. Aberrant activation of PI3K/Akt/mTOR signaling is a common event in T-ALL patients and portends a poor prognosis. Preclinical studies have highlighted that modulators of PI3K/Akt/mTOR signaling could have a therapeutic relevance in T-ALL. However, the best strategy for inhibiting this highly complex signal transduction pathway is still unclear, as the pharmaceutical companies have disclosed an impressive array of small molecules targeting this signaling network at different levels. Here, we demonstrate that a dual PI3K/PDK1 inhibitor, NVP-BAG956, displayed the most powerful cytotoxic affects against T-ALL cell lines and primary patients samples, when compared with a pan class I PI3K inhibitor (GDC-0941), an allosteric Akt inhibitor (MK-2206), an mTORC1 allosteric inhibitor (RAD-001), or an ATP-competitive mTORC1/mTORC2 inhibitor (KU63794). Moreover, we also document that combinations of some of the aforementioned drugs strongly synergized against T-ALL cells at concentrations well below their respective IC50. This observation indicates that vertical inhibition at different levels of the PI3K/Akt/mTOR network could be considered as a future innovative strategy for treating T-ALL patients.
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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.