azd-6244 has been researched along with Leukemia* in 2 studies
2 other study(ies) available for azd-6244 and Leukemia
| Article | Year |
|---|---|
Blockade of MEK/ERK signaling enhances sunitinib-induced growth inhibition and apoptosis of leukemia cells possessing activating mutations of the FLT3 gene.
The FMS-like tyrosine kinase 3 (FLT3) is a cell surface receptor tyrosine kinase. Activating mutations of this gene occur in nearly 30% of acute myelogenous leukemia (AML) patients. These mutations, in part, result in activation of mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. In this study, we found that AZD6244 (ARRY-142886), a novel inhibitor of MEK1/2 kinases, effectively inhibited the proliferation of acute biphenotypic leukemia MV4-11 and acute monocytic leukemia MOLM13 cells. The concentrations that inhibited 50% growth were approximately 0.3 and 1.2 microM, respectively, as measured by thymidine uptake on day 2 of culture. AZD6244 potently down-regulated the levels of phospho-ERK1/2 and its downstream effector, p-p70S6K, in the MV4-11 and MOLM13 cells as measured by Western blot analysis. Interestingly, when AZD6244 was combined with sunitinib, a FLT3 kinase inhibitor, growth inhibition and apoptosis of both MV4-11 and MOLM13 cells were synergistically enhanced in association with further down-regulation of phospho-ERK1/2 and p-p70S6K in these cells. Taken together, concomitant blockade of FLT3 and MEK signaling represents a promising treatment strategy for individuals with leukemia who possess activating mutations of FLT3. Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzimidazoles; Cell Proliferation; Female; fms-Like Tyrosine Kinase 3; Humans; Indoles; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Male; MAP Kinase Kinase 1; Middle Aged; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mutation; Pyrroles; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Sunitinib; Tumor Cells, Cultured | 2008 |
ZD6474 induces growth arrest and apoptosis of human leukemia cells, which is enhanced by concomitant use of a novel MEK inhibitor, AZD6244.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzimidazoles; Cell Proliferation; Drug Synergism; Humans; Leukemia; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Piperidines; Quinazolines; Tumor Cells, Cultured | 2007 |