Evidence map›Paper›PMID 25188519›Full record

ArticleCell death & disease2014

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

W Guo, R Liu, G Bhardwaj, J C Yang, C Changou, A-H Ma, A Mazloom, S Chintapalli, K Xiao, W Xiao and 7 more

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

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

  1. Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026
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  7. Review
  8. Review
  9. Article
  10. Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer.Journal of enzyme inhibition and medicinal chemistry · 2021
    Article
  11. Article
  12. Bruton's Tyrosine Kinase and Its Isoforms in Cancer.Frontiers in cell and developmental biology · 2021
    Review
  13. Targeting Solid Tumors With BTK Inhibitors.Frontiers in cell and developmental biology · 2021
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Adenosine-producing regulatory B cells in head and neck cancer.Cancer immunology, immunotherapy : CII · 2020
    Article
  19. Review
  20. Article
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

17 authors at 3 institutions in 2 countries.

W GuoDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
R LiuDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
G BhardwajDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
J C YangDepartment of Urology, University of California Davis, Sacramento, CA 95817, USA.
C ChangouDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
A-H MaDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
A MazloomDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
S Chintapalli1] Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA [2] Department of Physiology and Membrane Biology, University of California Davis, Sacramento, CA 95817, USA.
K XiaoDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
W XiaoDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
P KumaresanDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
E SanchezDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
C-T YehDepartment of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan, ROC.
C P EvansDepartment of Urology, University of California Davis, Sacramento, CA 95817, USA.
R Patterson1] Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA [2] Department of Physiology and Membrane Biology, University of California Davis, Sacramento, CA 95817, USA.
K S LamDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
H-J Kung1] Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA [2] Institute of Molecular and Genomic Medicine, National Health Research Institutes (NHRI), Miaoli County 35053, Taiwan, ROC.
University of California, Davis · USNational Health Research Institutes · TWTaipei Medical University-Shuang Ho Hospital · TW

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
Therapeutic Targeting Agents for Ovarian CancerR01CA115483 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI LAM, KIT S · 2005 to 2019
$5.5M
Targeting Agents for Human and Canine LymphomaU19CA113298 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI KURTH, MARK J. · 2005 to 2009
$5.4M
TYROSINE KINASES AND PROSTATE GROWTHR01DK052659 · NIDDK · UNIVERSITY OF CALIFORNIA DAVIS · PI KUNG, HSING-JIEN · 1997 to 2011
$2.9M
Tyrosine Kinases and Prostate CancerR01CA165263 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KUNG, HSING-JIEN · 2012 to 2016
$1.7M
Androgen Signaling and Coactivator Regulation in PCAR01CA150197 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KUNG, HSING-JIEN · 2010 to 2014
$1.7M
c-src inhibitors from novel encoded chemical librariesR01CA098116 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI LAM, KIT S · 2003 to 2007
$1.6M
Discovery of Death Ligands Against CancersR33CA160132 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LAM, KIT S · 2012 to 2014
$1.0M
NCI NIH HHS CA098116NCI NIH HHS CA150197NCI NIH HHS P30 CA093373NCI NIH HHS R01 CA098116NCI NIH HHS R01 CA115483NCI NIH HHS R01 CA150197NCI NIH HHS R01 CA165263NCI NIH HHS R33 CA160132NCI NIH HHS U19 CA113298NIDDK NIH HHS DK52659PHS HHS DOH102-TD-M-111-102001
6 · The paper itself

Abstract

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model.

Indexed as

Agammaglobulinaemia Tyrosine KinaseAnimalsAntineoplastic AgentsAutophagyBinding SitesCell Line, TumorCell ProliferationDocetaxelHumansImidazolesMaleMiceMice, NudeMolecular Docking SimulationPhospholipase C gammaPhosphorylationAgammaglobulinaemia Tyrosine KinaseAntineoplastic AgentsBMX protein, humanBTK protein, humanDocetaxelImidazolesN-(7-isobutyl-6-oxo-1-(3-(piperidin-1-yl)propyl)-5,6-dihydro-1H-imidazo(4,5-g)quinoxalin-2-yl)-4-(pyridin-4-yl)benzamidePhospholipase C gammaProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-aktQuinoxalinesRNA, Small InterferingSTAT3 Transcription FactorTaxoids

Identifiers

PMID25188519
PMCPMC4540187
OpenAlexW2088095756

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.