Evidence map›Paper›PMID 25878331›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015

Aurora A Kinase Inhibition Selectively Synergizes with Histone Deacetylase Inhibitor through Cytokinesis Failure in T-cell Lymphoma.

Kelly M Zullo, Yige Guo, Laurence Cooke, Xavier Jirau-Serrano, Michael Mangone, Luigi Scotto, Jennifer E Amengual, Yinghui Mao, Renu Nandakumar, Serge Cremers and 3 more

Abstract read
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In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.5field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 45 citations in OpenAlex.

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  6. GATA-3-dependent Gene Transcription is Impaired upon HDAC Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Kelly M ZulloDepartment of Medicine, Center for Lymphoid Malignancies, Columbia University Medical Center, New York, New York.
Yige GuoDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
Laurence CookeUniversity of Tennessee Health Science Center, West Cancer Center, Memphis, Tennessee.
Xavier Jirau-SerranoDepartment of Medicine, Center for Lymphoid Malignancies, Columbia University Medical Center, New York, New York.
Michael MangoneDepartment of Medicine, Center for Lymphoid Malignancies, Columbia University Medical Center, New York, New York.
Luigi ScottoDepartment of Medicine, Center for Lymphoid Malignancies, Columbia University Medical Center, New York, New York.
Jennifer E AmengualDepartment of Medicine, Center for Lymphoid Malignancies, Columbia University Medical Center, New York, New York.
Yinghui MaoDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
Renu NandakumarIrving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, New York.
Serge CremersDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, New York. Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, New York.
Jimmy DuongMailman School of Public Health, Columbia University, New York, New York.
Daruka MahadevanUniversity of Tennessee Health Science Center, West Cancer Center, Memphis, Tennessee.
Owen A O'ConnorDepartment of Medicine, Center for Lymphoid Malignancies, Columbia University Medical Center, New York, New York. owenoconnor@columbia.edu.
Columbia University Irving Medical Center · USUniversity of Tennessee Health Science Center · USColumbia University · US

Funding

Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Formin mDia Functions in MitosisR01GM089768 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAO, YINGHUI · 2011 to 2015
$1.6M
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1TR000040NIGMS NIH HHS R01 GM089768
6 · The paper itself

Abstract

purposeAurora A kinase (AAK) is expressed exclusively during mitosis, and plays a critical role in centrosome duplication and spindle formation. Alisertib is a highly selective AAK inhibitor that has demonstrated marked clinical activity of alisertib across a spectrum of lymphomas, though particularly in patients with T-cell lymphoma (TCL). We sought to compare and contrast the activity of alisertib in preclinical models of B-cell lymphoma (BCL) and TCL, and identify combinations worthy of clinical study. High-throughput screening of pralatrexate, the proteasome inhibitor (ixazomib), and the histone deacetylase (HDAC) inhibitor (romidepsin) revealed that only romidepsin synergized with alisertib, and only in models of TCL. We discovered that the mechanism of synergy between AAK inhibitors and HDAC inhibitors appears to be mediated through cytokinesis failure. EXPERIMENTAL

designA high-throughput screening approach was used to identify drugs that were potentially synergistic in combination with alisertib. Live-cell imaging was used to explore the mechanistic basis for the drug: drug interaction between alisertib and romidepsin. An in vivo xenograft TCL model was used to confirm in vitro results.

resultsIn vitro, alisertib exhibited concentration-dependent cytotoxicity in BCL and TCL cell lines. Alisertib was synergistic with romidepsin in a T-cell-specific fashion that was confirmed in vivo. Live-cell imaging demonstrated that the combination treatment resulted in profound cytokinesis failure.

conclusionsThese data strongly suggest that the combination of alisertib and romidepsin is highly synergistic in TCL through modulation of cytokinesis and merits clinical development.

Indexed as

AminopterinAnimalsAurora Kinase AAzepinesBoron CompoundsCell CycleCell Line, TumorCentrosomeCytokinesisDepsipeptidesDrug SynergismGlycineHistone Deacetylase InhibitorsHistone DeacetylasesHumansInhibitory Concentration 5010-propargyl-10-deazaaminopterinAminopterinAurora Kinase AAzepinesBoron CompoundsDepsipeptidesGlycineHistone Deacetylase InhibitorsHistone DeacetylasesixazomibMLN 8237Protein Kinase InhibitorsPyrimidinesromidepsin

Identifiers

PMID25878331
PMCPMC4581881
OpenAlexW2050627026

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

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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.