Evidence map›Paper›PMID 27256378›Full record

ArticleMolecular cancer therapeutics2016

Bruton's Tyrosine Kinase Inhibitors Prevent Therapeutic Escape in Breast Cancer Cells.

Xianhui Wang, Jason Wong, Christopher J Sevinsky, Leila Kokabee, Faiza Khan, Yan Sun, Douglas S Conklin

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 13% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

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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

7 authors at 1 institution in 2 countries.

Xianhui WangCancer Research Center and Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, New York.
Jason WongCancer Research Center and Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, New York.
Christopher J SevinskyCancer Research Center and Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, New York.
Leila KokabeeCancer Research Center and Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, New York. Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.
Faiza KhanCancer Research Center and Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, New York.
Yan SunCancer Research Center and Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, New York.
Douglas S ConklinCancer Research Center and Department of Biomedical Sciences, State University of New York, University at Albany, Rensselaer, New York. dconklin@albany.edu.
Albany State University · US

Funding

NR1D1 pathway in breast cancerR01CA136658 · NCI · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI CONKLIN, DOUGLAS S. · 2009 to 2012
$1.2M
NCI NIH HHS R01 CA136658
6 · The paper itself

Abstract

We have reported that a novel isoform of BTK (BTK-C) expressed in breast cancer protects these cells from apoptosis. In this study, we show that recently developed inhibitors of BTK, such as ibrutinib (PCI-32765), AVL-292, and CGI-1746, reduce breast cancer cell survival and prevent drug-resistant clones from arising. Ibrutinib treatment impacts HER2(+) breast cancer cell viability at lower concentrations than the established breast cancer therapeutic lapatinib. In addition to inhibiting BTK, ibrutinib, but not AVL-292 and CGI-1746, efficiently blocks the activation of EGFR, HER2, ErbB3, and ErbB4. Consequently, the activation of AKT and ERK signaling pathways are also blocked leading to a G1-S cell-cycle delay and increased apoptosis. Importantly, inhibition of BTK prevents activation of the AKT signaling pathway by NRG or EGF that has been shown to promote growth factor-driven lapatinib resistance in HER2(+) breast cancer cells. HER2(+) breast cancer cell proliferation is blocked by ibrutinib even in the presence of these factors. AVL-292, which has no effect on EGFR family activation, prevents NRG- and EGF-dependent growth factor-driven resistance to lapatinib in HER2(+) breast cancer cells. In vivo, ibrutinib inhibits HER2(+) xenograft tumor growth. Consistent with this, immunofluorescence analysis of xenograft tumors shows that ibrutinib reduces the phosphorylation of HER2, BTK, Akt, and Erk and histone H3 and increases cleaved caspase-3 signals. As BTK-C and HER2 are often coexpressed in human breast cancers, these observations indicate that BTK-C is a potential therapeutic target and that ibrutinib could be an effective drug especially for HER2(+) breast cancer. Mol Cancer Ther; 15(9); 2198-208. ©2016 AACR.

Indexed as

AdenineAgammaglobulinaemia Tyrosine KinaseAnimalsAntineoplastic AgentsApoptosisBreast NeoplasmsCell Line, TumorCell ProliferationCell SurvivalDisease Models, AnimalEpidermal Growth FactorErb-b2 Receptor Tyrosine KinasesFemaleGene ExpressionHumansLapatinibAdenineAgammaglobulinaemia Tyrosine KinaseAntineoplastic AgentsBTK protein, humanBtk protein, mouseEpidermal Growth FactorErb-b2 Receptor Tyrosine KinasesibrutinibLapatinibNeuregulin-1PiperidinesProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-aktPyrazolesPyrimidinesQuinazolines

Identifiers

PMID27256378
PMCPMC5145257
OpenAlexW2416897715

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.