ArticleOncotarget2015
The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression.
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, 39 citations in OpenAlex.
- Integrated Genomic and Transcriptomic Profiling of Isolated Trisomies in AML Reveals Cell Cycle Dysregulation and Therapeutic Vulnerabilities.Journal of cellular and molecular medicine · 2025Article
- Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer.Biomedicines · 2024Review
- Organ-specific off-target effects of Pim/ZIP kinase inhibitors suggest lack of contractile Pim kinase activity in prostate, bladder, and vascular smooth muscle.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Kinase-independent role of mTOR and on-/off-target effects of an mTOR kinase inhibitor.Leukemia · 2023Article
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- HSF1 is a driver of leukemia stem cell self-renewal in acute myeloid leukemia.Nature communications · 2022Article
- Dual Kinase Targeting in Leukemia.Cancers · 2021Review
- Directly imaging the localisation and photosensitization properties of the pan-mTOR inhibitor, AZD2014, in living cancer cells.Journal of photochemistry and photobiology. B, Biology · 2020Article
- Article
- Human papillomavirus insertions identify the PIM family of serine/threonine kinases as targetable driver genes in head and neck squamous cell carcinoma.Cancer letters · 2020Article
- Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy.iScience · 2019Article
- Inhibition of FAO in AML co-cultured with BM adipocytes: mechanisms of survival and chemosensitization to cytarabine.Scientific reports · 2018Article
- PIM Kinase as an Executional Target in Cancer.Journal of cancer prevention · 2018Review
- A novel, dual pan-PIM/FLT3 inhibitor SEL24 exhibits broad therapeutic potential in acute myeloid leukemia.Oncotarget · 2018Article
- Article
- From Waldenström's macroglobulinemia to aggressive diffuse large B-cell lymphoma: a whole-exome analysis of abnormalities leading to transformation.Blood cancer journal · 2017Article
- Targeting mantle cell lymphoma metabolism and survival through simultaneous blockade of mTOR and nuclear transporter exportin-1.Oncotarget · 2017Article
- Protein profiling identifies mTOR pathway modulation and cytostatic effects of Pim kinase inhibitor, AZD1208, in acute myeloid leukemia.Leukemia & lymphoma · 2016Article
- Targeting mTOR for the treatment of B cell malignancies.British journal of clinical pharmacology · 2016Review
- miR-34b Targets HSF1 to Suppress Cell Survival in Acute Myeloid Leukemia.Oncology research · 2016Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Mammalian target of rapamycin (mTOR) signaling is a critical pathway in the biology of acute myeloid leukemia (AML). Proviral integration site for moloney murine leukemia virus (PIM) serine/threonine kinase signaling takes part in various pathways exerting tumorigenic properties. We hypothesized that the combination of a PIM kinase inhibitor with an mTOR inhibitor might have complementary growth-inhibitory effects against AML. The simultaneous inhibition of the PIM kinase by pan-PIM inhibitor AZD1208 and of mTOR by selective mTORC1/2 dual inhibitor AZD2014 exerted anticancer properties in AML cell lines and in cells derived from primary AML samples with or without supportive stromal cell co-culture, leading to suppressed proliferation and increased apoptosis. The combination of AZD1208 and AZD2014 rapidly activated AMPKα, a negative regulator of translation machinery through mTORC1/2 signaling in AML cells; profoundly inhibited AKT and 4EBP1 activation; and suppressed polysome formation. Inhibition of both mTOR and PIM counteracted induction of heat-shock family proteins, uncovering the master negative regulation of heat shock factor 1 (HSF1), the dominant transcription factor controlling cellular stress responses. The novel combination of the dual mTOR inhibitor and pan-PIM inhibitor synergistically inhibited AML growth by effectively reducing protein synthesis through heat shock factor pathway suppression.
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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.