ArticleOncotarget2012
A combination of temsirolimus, an allosteric mTOR inhibitor, with clofarabine as a new therapeutic option for patients with acute myeloid leukemia.
Article in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- Ellagic acid inhibited cervical cancer growth via blocking the AKT/mTOR/STAT3 pathway.Archives of medical science : AMS · 2026Article
- Understanding the Link between Inflammasome and Apoptosis through the Response of THP-1 Cells against Drugs Using Droplet-Based Microfluidics.ACS omega · 2022Article
- How Do Modulators Affect the Orthosteric and Allosteric Binding Pockets?ACS chemical neuroscience · 2022Article
- Article
- Targeting signaling and apoptotic pathways involved in chemotherapeutic drug-resistance of hematopoietic cells.Oncotarget · 2017Article
- Review
- Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer.Cellular oncology (Dordrecht, Netherlands) · 2017Review
- Understanding of leukemic stem cells and their clinical implications.Molecular cancer · 2017Review
- Synergistic antitumor activity of rapamycin and EF24 via increasing ROS for the treatment of gastric cancer.Redox biology · 2016Article
- Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia.Oncotarget · 2016Article
- Improving nelarabine efficacy in T cell acute lymphoblastic leukemia by targeting aberrant PI3K/AKT/mTOR signaling pathway.Journal of hematology & oncology · 2016Article
- mTOR inhibitors in urinary bladder cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.Frontiers in oncology · 2016Review
- Article
- Article
- The novel dual PI3K/mTOR inhibitor NVP-BGT226 displays cytotoxic activity in both normoxic and hypoxic hepatocarcinoma cells.Oncotarget · 2015Article
- Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-β-cyclodextrin: Involvement of p53 and Fas receptor ligand complex.Scientific reports · 2015Article
- Triple Akt inhibition as a new therapeutic strategy in T-cell acute lymphoblastic leukemia.Oncotarget · 2015Article
- The interplay of autophagy and β-Catenin signaling regulates differentiation in acute myeloid leukemia.Cell death discovery · 2015Article
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling through the phosphatidylinositol 3-kinase (PI3K) pathway and its downstream effectors, Akt and mechanistic target of rapamycin (mTOR), is aberrantly activated in acute myeloid leukemia (AML) patients, where it contributes to leukemic cell proliferation, survival, and drug-resistance. Thus, inhibiting mTOR signaling in AML blasts could enhance their sensitivity to cytotoxic agents. Preclinical data also suggest that allosteric mTOR inhibition with rapamycin impaired leukemia initiating cells (LICs) function. In this study, we assessed the therapeutic potential of a combination consisting of temsirolimus [an allosteric mTOR complex 1 (mTORC1) inhibitor] with clofarabine, a nucleoside analogue with potent inhibitory effects on both ribonucleotide reductase and DNA polymerase. The drug combination (CLO-TOR) displayed synergistic cytotoxic effects against a panel of AML cell lines and primary cells from AML patients. Treatment with CLO-TOR induced a G₀/G₁-phase cell cycle arrest, apoptosis, and autophagy. CLO-TOR was pro-apoptotic in an AML patient blast subset (CD34⁺/CD38⁻/CD123⁺), which is enriched in putative leukemia initiating cells (LICs). In summary, the CLO-TOR combination could represent a novel valuable treatment for AML patients, also in light of its efficacy against LICs.
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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.