ArticleNature medicine2010
Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor.
Article in Nature medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 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
206 citing papers in PubMed, 334 citations in OpenAlex.
- A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161.Investigational new drugs · 2022Trial
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- mTOR inhibition promotes ATRA-induced cancer cell differentiation by overcoming a metabolic hyperactive state.Journal of translational medicine · 2026Article
- In Vitro Inhibition ofPathogens (Basel, Switzerland) · 2025Article
- AKT/mTOR as a targetable hub to overcome multimodal resistance to EGFR inhibitors in oesophageal squamous cell carcinoma.British journal of cancer · 2025Article
- WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain acute myeloid leukaemia growth.Nature communications · 2025Article
- CRISPR-mediated reversion of oncogenic KRAS mutation results in increased proliferation and reveals independent roles of Ras and mTORC2 in the migration of A549 lung cancer cells.Molecular biology of the cell · 2023Article
- Prior Treatment with AICAR Causes the Selective Phosphorylation of mTOR Substrates in C2C12 Cells.Current issues in molecular biology · 2023Article
- Review
- Review
- Microphysiological model of PIK3CA-driven vascular malformations reveals a role of dysregulated Rac1 and mTORC1/2 in lesion formation.Science advances · 2023Article
- mTORC2 Is Activated under Hypoxia and Could Support Chronic Myeloid Leukemia Stem Cells.International journal of molecular sciences · 2023Article
- Autolysosomal activation combined with lysosomal destabilization efficiently targets myeloid leukemia cells for cell death.Frontiers in oncology · 2023Article
- Novel pharmacological and dietary approaches to target mTOR in B-cell acute lymphoblastic leukemia.Frontiers in oncology · 2023Article
- Spatial patterns of the cap-binding complex eIF4F in human melanoma cells.Computational and structural biotechnology journal · 2023Article
- Lomitapide, a cholesterol-lowering drug, is an anticancer agent that induces autophagic cell death via inhibiting mTOR.Cell death & disease · 2022Article
- Identification of 4-Anilinoquin(az)oline as a Cell-Active Protein Kinase Novel 3 (PKN3) Inhibitor Chemotype.ChemMedChem · 2022Article
- Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches.Pharmaceutics · 2022Review
- Detoxified pneumolysin derivative ΔA146Ply inhibits autophagy and induces apoptosis in acute myeloid leukemia cells by activating mTOR signaling.Experimental & molecular medicine · 2022Article
- Targeting autophagy in disease: established and new strategies.Autophagy · 2022Article
146 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
Abstract
Targeting the mammalian target of rapamycin (mTOR) protein is a promising strategy for cancer therapy. The mTOR kinase functions in two complexes, TORC1 (target of rapamycin complex-1) and TORC2 (target of rapamycin complex-2); however, neither of these complexes is fully inhibited by the allosteric inhibitor rapamycin or its analogs. We compared rapamycin with PP242, an inhibitor of the active site of mTOR in both TORC1 and TORC2 (hereafter referred to as TORC1/2), in models of acute leukemia harboring the Philadelphia chromosome (Ph) translocation. We demonstrate that PP242, but not rapamycin, causes death of mouse and human leukemia cells. In vivo, PP242 delays leukemia onset and augments the effects of the current front-line tyrosine kinase inhibitors more effectively than does rapamycin. Unexpectedly, PP242 has much weaker effects than rapamycin on the proliferation and function of normal lymphocytes. PI-103, a less selective TORC1/2 inhibitor that also targets phosphoinositide 3-kinase (PI3K), is more immunosuppressive than PP242. These findings establish that Ph(+) transformed cells are more sensitive than normal lymphocytes to selective TORC1/2 inhibitors and support the development of such inhibitors for leukemia therapy.
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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.