fostamatinib and Leukemia--Myeloid--Acute

fostamatinib has been researched along with Leukemia--Myeloid--Acute* in 4 studies

Other Studies

4 other study(ies) available for fostamatinib and Leukemia--Myeloid--Acute

ArticleYear
Heterogeneity of Patient-Derived Acute Myeloid Leukemia Cells Subjected to SYK In Vitro Inhibition.
    International journal of molecular sciences, 2022, Nov-25, Volume: 23, Issue:23

    Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a dismal prognosis. The cytoplasmic spleen tyrosine kinase (SYK) is highly expressed by hematopoietic cells and has emerged as a potential therapeutic target. In this study, we evaluated the in vitro antileukemic effects of five SYK inhibitors, fostamatinib, entospletinib, cerdulatinib, TAK-659, and RO9021, in a consecutive AML patient cohort. All inhibitors demonstrated a concentration-dependent antiproliferative effect, although there was considerable heterogeneity among patients. For fostamatinib and TAK-659, the antiproliferative effects were significantly higher in

    Topics: Aminopyridines; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Protein Kinase Inhibitors; Signal Transduction; Syk Kinase

2022
The target landscape of clinical kinase drugs.
    Science (New York, N.Y.), 2017, 12-01, Volume: 358, Issue:6367

    Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.

    Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cytokines; Drug Discovery; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Lung Neoplasms; Mice; Molecular Targeted Therapy; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Proteomics; Xenograft Model Antitumor Assays

2017
Can treating the SYK cell cure leukemia?
    Cancer cell, 2009, Oct-06, Volume: 16, Issue:4

    Targeted therapy has remained elusive for most acute myeloid leukemia patients. In this issue of Cancer Cell, Stegmaier and colleagues identify SYK as a key mediator of the differentiation block seen in this disease. Their data suggest that SYK inhibition may be an effective therapy for a significant proportion of AMLs.

    Topics: Aminopyridines; Animals; Antineoplastic Agents; Cell Differentiation; Cell Proliferation; Dose-Response Relationship, Drug; Gefitinib; Gene Expression Regulation, Leukemic; Genomics; Humans; Inhibitory Concentration 50; Intracellular Signaling Peptides and Proteins; Leukemia, Myeloid, Acute; Morpholines; Oxazines; Phosphorylation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proteomics; Pyridines; Pyrimidines; Quinazolines; Syk Kinase; Time Factors; Tyrosine

2009
Proteomic and genetic approaches identify Syk as an AML target.
    Cancer cell, 2009, Oct-06, Volume: 16, Issue:4

    Cell-based screening can facilitate the rapid identification of compounds inducing complex cellular phenotypes. Advancing a compound toward the clinic, however, generally requires the identification of precise mechanisms of action. We previously found that epidermal growth factor receptor (EGFR) inhibitors induce acute myeloid leukemia (AML) differentiation via a non-EGFR mechanism. In this report, we integrated proteomic and RNAi-based strategies to identify their off-target, anti-AML mechanism. These orthogonal approaches identified Syk as a target in AML. Genetic and pharmacological inactivation of Syk with a drug in clinical trial for other indications promoted differentiation of AML cells and attenuated leukemia growth in vivo. These results demonstrate the power of integrating diverse chemical, proteomic, and genomic screening approaches to identify therapeutic strategies for cancer.

    Topics: Aminopyridines; Animals; Antineoplastic Agents; Cell Differentiation; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Gefitinib; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genomics; HL-60 Cells; Humans; Inhibitory Concentration 50; Intracellular Signaling Peptides and Proteins; Leukemia, Myeloid, Acute; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Morpholines; Oxazines; Phosphorylation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proteomics; Pyridines; Pyrimidines; Quinazolines; RNA Interference; Syk Kinase; Tandem Mass Spectrometry; Time Factors; Tumor Cells, Cultured; Tyrosine; U937 Cells; Xenograft Model Antitumor Assays

2009