ArticleBlood2009
Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed.
- Trial
- Review
- Dasatinib Dose Optimization Based on Therapeutic Drug Monitoring in Patients with Chronic-Phase Chronic Myeloid Leukemia.Drug design, development and therapy · 2025Article
- Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer.Vaccines · 2022Review
- KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data.Nature communications · 2022Article
- Article
- Therapeutic Drug Monitoring and Individualized Medicine of Dasatinib: Focus on Clinical Pharmacokinetics and Pharmacodynamics.Frontiers in pharmacology · 2021Review
- Response and Resistance to BCR-ABL1-Targeted Therapies.Cancer cell · 2020Review
- Novel approaches to treating advanced systemic mastocytosis.Clinical pharmacology : advances and applications · 2019Review
- Article
- What Is the Optimal Dose and Schedule for Dasatinib in Chronic Myeloid Leukemia: Two Case Reports and Review of the Literature.Oncology research · 2016Review
- Transient rRNA synthesis inhibition with CX-5461 is sufficient to elicit growth arrest and cell death in acute lymphoblastic leukemia cells.Oncotarget · 2015Article
- Sustained inhibition of STAT5, but not JAK2, is essential for TKI-induced cell death in chronic myeloid leukemia.Leukemia · 2015Article
- MEK-dependent negative feedback underlies BCR-ABL-mediated oncogene addiction.Cancer discovery · 2014Article
- A screening-based approach to circumvent tumor microenvironment-driven intrinsic resistance to BCR-ABL+ inhibitors in Ph+ acute lymphoblastic leukemia.Journal of biomolecular screening · 2014Article
- KIT signaling governs differential sensitivity of mature and primitive CML progenitors to tyrosine kinase inhibitors.Cancer research · 2013Article
- Kinase inhibitor therapy in CML: it's what's inside that counts.Oncotarget · 2013Article
- Nilotinib shows prolonged intracellular accumulation upon pulse-exposure: a novel mechanism for induction of apoptosis in CML cells.Leukemia · 2013Article
- The small molecules AZD0530 and dasatinib inhibit dengue virus RNA replication via Fyn kinase.Journal of virology · 2013Article
- Threshold levels of ABL tyrosine kinase inhibitors retained in chronic myeloid leukemia cells determine their commitment to apoptosis.Cancer research · 2013Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Pioneering work with the Bcr-Abl inhibitor, imatinib, demonstrated a requirement for constant Bcr-Abl inhibition to achieve maximal therapeutic benefit in treating chronic myeloid leukemia (CML), establishing a paradigm that has guided further drug development for this disease. Surprisingly, the second-generation Bcr-Abl inhibitor, dasatinib, was reported to be clinically effective with once-daily dosing, despite a short (3- to 5-hour) plasma half-life. Consistent with this observation, dasatinib treatment of progenitor cells from chronic-phase CML patients for 4 hours, followed by washout, or continuously for 72 hours both resulted in an induction of apoptosis and a reduction in the number of clonogenic cells. Such acute treatments with clinically achievable dasatinib concentrations also irreversibly committed Bcr-Abl+ CML cell lines to apoptotic cell death. Potent transient Bcr-Abl inhibition using the alternative inhibitor, nilotinib, also resulted in cell death. These findings demonstrate that in vitro assays designed to model in vivo pharmacokinetics can predict clinical efficacy. Furthermore, they challenge the widely held notion that continuous target inhibition is required for optimal efficacy of kinase inhibitors.
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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.