ArticleOncotarget2015
mTOR kinase inhibitors synergize with histone deacetylase inhibitors to kill B-cell acute lymphoblastic leukemia cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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
21 citing papers in PubMed, 34 citations in OpenAlex.
- CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL.International journal of molecular sciences · 2026Article
- Bridging the Gap: Cost-Effective Strategies for Detecting Ph-Like B-Lineage ALL in Resource-Limited Settings.Molecular diagnosis & therapy · 2025Review
- Getting the right combination to break the epigenetic code.Nature reviews. Clinical oncology · 2025Review
- Article
- The Current Genomic and Molecular Landscape of Philadelphia-like Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Review
- Targeting mTOR in Acute Lymphoblastic Leukemia.Cells · 2019Review
- Article
- Snail determines the therapeutic response to mTOR kinase inhibitors by transcriptional repression of 4E-BP1.Nature communications · 2017Article
- HDAC inhibition as a treatment concept to combat temsirolimus-resistant bladder cancer cells.Oncotarget · 2017Article
- The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL.Leukemia · 2017Article
- mTORC1 Inhibition Induces Resistance to Methotrexate and 6-Mercaptopurine in PhMolecular cancer therapeutics · 2017Article
- Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation.Molecular cancer therapeutics · 2017Article
- Control of B lymphocyte development and functions by the mTOR signaling pathways.Cytokine & growth factor reviews · 2017Review
- Targeting mTOR for the treatment of B cell malignancies.British journal of clinical pharmacology · 2016Review
- HDACs and HDAC Inhibitors in Cancer Development and Therapy.Cold Spring Harbor perspectives in medicine · 2016Review
- MLN0128, a novel mTOR kinase inhibitor, disrupts survival signaling and triggers apoptosis in AML and AML stem/ progenitor cells.Oncotarget · 2016Article
- mTOR signaling: new networks for ALL.Blood · 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
- mTORC signaling in hematopoiesis.International journal of hematology · 2016Review
- Inhibitors of mTOR in aging and cancer.Oncotarget · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
High activity of the mechanistic target of rapamycin (mTOR) is associated with poor prognosis in pre-B-cell acute lymphoblastic leukemia (B-ALL), suggesting that inhibiting mTOR might be clinically useful. However, emerging data indicate that mTOR inhibitors are most effective when combined with other target agents. One strategy is to combine with histone deacetylase (HDAC) inhibitors, since B-ALL is often characterized by epigenetic changes that silence the expression of pro-apoptotic factors. Here we tested combinations of mTOR and pan-HDAC inhibitors on B-ALL cells, including both Philadelphia chromosome-positive (Ph+) and non-Ph cell lines. We found that mTOR kinase inhibitors (TOR-KIs) synergize with HDAC inhibitors to cause apoptosis in B-ALL cells and the effect is greater when compared to rapamycin plus HDAC inhibitors. The combination of TOR-KIs with the clinically approved HDAC inhibitor vorinostat increased apoptosis in primary pediatric B-ALL cells in vitro. Mechanistically, TOR-KI and HDAC inhibitor combinations increased expression of pro-death genes, including targets of the Forkhead Box O (FOXO) transcription factors, and increased sensitivity to apoptotic triggers at the mitochondria. These findings suggest that targeting epigenetic factors can unmask the cytotoxic potential of TOR-KIs towards B-ALL cells.
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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.