ArticleMolecular cancer therapeutics2010
Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- O-acetylated N-acetylneuraminic acid as a novel target for therapy in human pre-B acute lymphoblastic leukemia.The Journal of experimental medicine · 2013Trial
- MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia.Leukemia · 2013Trial
- Advances in Targeting BCR-ABLMolecules (Basel, Switzerland) · 2026Review
- LncRNA PAINT is associated with aggressive prostate cancer and dysregulation of cancer hallmark genes.International journal of cancer · 2021Article
- Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.PloS one · 2021Article
- Targeting CXCR4 in AML and ALL.Frontiers in oncology · 2020Review
- Treatment of B-cell precursor acute lymphoblastic leukemia with the Galectin-1 inhibitor PTX008.Journal of experimental & clinical cancer research : CR · 2018Article
- On the importance of composite protein multiple ligand interactions in protein pockets.Journal of computational chemistry · 2017Article
- Direct and indirect targeting of MYC to treat acute myeloid leukemia.Cancer chemotherapy and pharmacology · 2015Article
- Article
- Glutaminase activity determines cytotoxicity of L-asparaginases on most leukemia cell lines.Leukemia research · 2015Article
- B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3.Oncotarget · 2015Article
- Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells.Leukemia · 2015Article
- Phosphoflow-Based Evaluation of Mek Inhibitors as Small-Molecule Therapeutics for B-Cell Precursor Acute Lymphoblastic Leukemia.PloS one · 2015Article
- Therapy of chronic myeloid leukemia: twilight of the imatinib era?ISRN oncology · 2014Review
- Adipocytes cause leukemia cell resistance to L-asparaginase via release of glutamine.Cancer research · 2013Article
- Pediatric relapsed or refractory leukemia: new pharmacotherapeutic developments and future directions.Drugs · 2013Review
- Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells.BMC genomics · 2012Article
- Bioinformatics and variability in drug response: a protein structural perspective.Journal of the Royal Society, Interface · 2012Review
- Treatment of human pre-B acute lymphoblastic leukemia with the Aurora kinase inhibitor PHA-739358 (Danusertib).Molecular cancer · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The emergence of resistance to tyrosine kinase inhibitors due to point mutations in Bcr/Abl is a challenging problem for Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) patients, especially for those with the T315I mutation, against which neither nilotinib or dasatinib shows significant activity. VX-680 is a pan-Aurora kinase inhibitor active against all Bcr/Abl proteins but has not been extensively examined in preclinical models of Ph-positive ALL. Here, we have tested VX-680 for the treatment of Bcr/Abl-positive ALL when leukemic cells are protected by the presence of stroma. Under these conditions, VX-680 showed significant effects on primary human Ph-positive ALL cells both with and without the T315I mutation, including ablation of tyrosine phosphorylation downstream of Bcr/Abl, decreased viability, and induction of apoptosis. However, drug treatment of human Ph-positive ALL cells for 3 days followed by drug removal allowed the outgrowth of abnormal cells 21 days later, and on culture of mouse Bcr/Abl ALL cells on stroma with lower concentrations of VX-680, drug-resistant cells emerged. Combined treatment of human ALL cells lacking the T315I mutation with both VX-680 and dasatinib caused significantly more cytotoxicity than each drug alone. We suggest that use of VX-680 together with a second effective drug as first-line treatment for Ph-positive ALL is likely to be safer and more useful than second-line treatment with VX-680 as monotherapy for drug-resistant T315I Ph-positive ALL.
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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.