ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
Cotreatment with vorinostat enhances activity of MK-0457 (VX-680) against acute and chronic myelogenous leukemia cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 68 citations in OpenAlex.
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- A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.Oncogenesis · 2021Article
- Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy.Molecular cancer · 2021Review
- HDAC Inhibitors in Acute Myeloid Leukemia.Cancers · 2019Review
- An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by disrupting mitotic progression.Cancer medicine · 2018Article
- FusionPathway: Prediction of pathways and therapeutic targets associated with gene fusions in cancer.PLoS computational biology · 2018Article
- Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation.Scientific reports · 2016Article
- The Aurora kinase inhibitors in cancer research and therapy.Journal of cancer research and clinical oncology · 2016Review
- Proteasome inhibitor MG-132 enhances histone deacetylase inhibitor SAHA-induced cell death of chronic myeloid leukemia cells by an ROS-mediated mechanism and downregulation of the Bcr-Abl fusion protein.Oncology letters · 2015Article
- Rational Combinations of Targeted Agents in AML.Journal of clinical medicine · 2015Review
- Combining the pan-aurora kinase inhibitor AMG 900 with histone deacetylase inhibitors enhances antitumor activity in prostate cancer.Cancer medicine · 2014Article
- Histone deacetylase inhibitor (HDACI) mechanisms of action: emerging insights.Pharmacology & therapeutics · 2014Review
- VX680 suppresses the growth of HepG2 cells and enhances the chemosensitivity to cisplatin.Oncology letters · 2014Article
- Genetic syndromes caused by mutations in epigenetic genes.Human genetics · 2013Review
- Targeting Aurora A kinase activity with the investigational agent alisertib increases the efficacy of cytarabine through a FOXO-dependent mechanism.International journal of cancer · 2012Article
- Linking epithelial-to-mesenchymal-transition and epigenetic modifications.Seminars in cancer biology · 2012Review
- In vitro evaluation of the Aurora kinase inhibitor VX-680 for Hepatoblastoma.Pediatric surgery international · 2012Article
- Overcoming CML acquired resistance by specific inhibition of Aurora A kinase in the KCL-22 cell model.Carcinogenesis · 2012Article
- The Interface between BCR-ABL-Dependent and -Independent Resistance Signaling Pathways in Chronic Myeloid Leukemia.Leukemia research and treatment · 2012Article
- The novel Aurora A kinase inhibitor MLN8237 is active in resistant chronic myeloid leukaemia and significantly increases the efficacy of nilotinib.Journal of cellular and molecular medicine · 2011Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
purposeWe determined the effects of vorinostat (suberoylanalide hydroxamic acid) and/or MK-0457 (VX-680), an Aurora kinase inhibitor on the cultured human (HL-60, OCI-AML3, and K562) and primary acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML), as well as on the murine pro-B BaF3 cells with ectopic expression of the unmutated and mutant forms of Bcr-Abl. EXPERIMENTAL
designFollowing exposure to MK-0457 and/or vorinostat, apoptosis, loss of viability, as well as activity and levels of Aurora kinase and Bcr-Abl proteins were determined.
resultsTreatment with MK-0457 decreased the phosphorylation of Aurora kinase substrates including serine (S)10 on histone H3 and survivin, and led to aberrant mitosis, DNA endoreduplication as well as apoptosis of the cultured human acute leukemia HL-60, OCI-AML3, and K562 cells. Combined treatment with vorinostat and MK-0457 resulted in greater attenuation of Aurora and Bcr-Abl (in K562) kinase activity and levels as well as synergistically induced apoptosis of OCI-AML3, HL-60, and K562 cells. MK-0457 plus vorinostat also induced synergistic apoptosis of BaF3 cells with ectopic overexpression of wild-type or mutant Bcr-Abl. Finally, cotreatment with MK-0457 and vorinostat induced more loss of viability of primary AML and imatinib-refractory CML than treatment with either agent alone, but exhibited minimal toxicity to normal CD34+ progenitor cells.
conclusionsCombined in vitro treatment with MK-0457 and vorinostat is highly active against cultured and primary leukemia cells. These findings merit in vivo testing of the combination against human AML and CML cells, especially against imatinib mesylate-resistant Bcr-AblT315I-expressing CML Cells.
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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.