Evidence map›Paper›PMID 25798061›Full record

ArticleInternational journal of biological sciences2015

MEK inhibitor PD-0325901 overcomes resistance to CK2 inhibitor CX-4945 and exhibits anti-tumor activity in head and neck cancer.

Yansong Bian, Jiawei Han, Vishnu Kannabiran, Suresh Mohan, Hui Cheng, Jay Friedman, Luo Zhang, Carter VanWaes, Zhong Chen

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

Article in International journal of biological sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 43 citations in OpenAlex.

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  11. Hypermethylation of theCancer management and research · 2020
    Article
  12. Role of protein kinase CK2 in antitumor drug resistance.Journal of experimental & clinical cancer research : CR · 2019
    Review
  13. Protein Kinase CK2, a Potential Therapeutic Target in Carcinoma ManagementAsian Pacific journal of cancer prevention : APJCP · 2019
    Review
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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

9 authors at 3 institutions in 3 countries.

Yansong Bian1. Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA;
Jiawei Han1. Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA; ; 2. Department of Otolaryngology Head and Neck Surgery, National Key Discipline, Key Laboratory of Otolaryngology Head and Neck Surgery of the Ministry of Education, Beijing Tongren Hospital, Capital Medical University, Beijing, China;
Vishnu Kannabiran1. Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA; ; 3. NIH Clinical Research Training Program-NIH Medical Research Scholars Program, Bethesda, MD, USA.
Suresh Mohan1. Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA; ; 3. NIH Clinical Research Training Program-NIH Medical Research Scholars Program, Bethesda, MD, USA.
Hui Cheng1. Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA;
Jay Friedman1. Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA;
Luo Zhang2. Department of Otolaryngology Head and Neck Surgery, National Key Discipline, Key Laboratory of Otolaryngology Head and Neck Surgery of the Ministry of Education, Beijing Tongren Hospital, Capital Medical University, Beijing, China;
Carter VanWaes1. Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA;
Zhong Chen1. Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA;
National Institute on Deafness and Other Communication Disorders · USBeijing Tongren Hospital · CNCapital Medical University · CN

Funding

Genomics and Proteomics of Head and Neck CancerZIADC000074 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$11.1M
Signal and Transcription Factor Network interactions in Head and Neck CancerZIADC000073 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$9.1M
Intramural NIH HHS ZIA DC000073Intramural NIH HHS ZIA DC000074
6 · The paper itself

Abstract

The serine-threonine kinase CK2 exhibits genomic alterations and aberrant overexpression in human head and neck squamous cell carcinomas (HNSCC). Here, we investigated the effects of CK2 inhibitor CX-4945 in human HNSCC cell lines and xenograft models. The IC50's of CX-4945 for 9 UM-SCC cell lines measured by MTT assay ranged from 3.4-11.9 μM. CX-4945 induced cell cycle arrest and cell death measured by DNA flow cytometry, and inhibited prosurvival mediators phospho-AKT and p-S6 in UM-SCC1 and UM-SCC46 cells. CX-4945 decreased NF-κB and Bcl-XL reporter gene activities in both cell lines, but upregulated proapoptotic TP53 and p21 reporter activities, and induced phospho-ERK, AP-1, and IL-8 activity in UM-SCC1 cells. CX-4945 exhibited modest anti-tumor activity in UM-SCC1 xenografts. Tumor immunostaining revealed significant inhibition of PI3K-Akt-mTOR pathway and increased apoptosis marker TUNEL, but also induced p-ERK, c-JUN, JUNB, FOSL1 and proliferation (Ki67) markers, as a possible resistance mechanism. To overcome the drug resistance, we tested MEK inhibitor PD-0325901 (PD-901), which inhibited ERK-AP-1 activation alone and in combination with CX-4945. PD-901 alone displayed significant anti-tumor effects in vivo, and the combination of PD-901 and CX-4945 slightly enhanced anti-tumor activity when compared with PD-901 alone. Immunostaining of tumor specimens after treatment revealed inhibition of p-AKT S129 and p-AKT T308 by CX-4945, and inhibition of p-ERK T202/204 and AP-1 family member FOSL-1 by PD-901. Our study reveals a drug resistance mechanism mediated by the MEK-ERK-AP-1 pathway in HNSCC. MEK inhibitor PD-0325901 is active in HNSCC resistant to CX-4945, meriting further clinical investigation.

Indexed as

AnimalsBenzamidesBlotting, WesternCasein Kinase IICell Line, TumorDiphenylamineFemaleFlow CytometryFos-Related Antigen 1Head and Neck NeoplasmsHumansJNK Mitogen-Activated Protein KinasesMiceMice, Inbred BALB CMice, SCIDNaphthyridinesBenzamidesCasein Kinase IIDiphenylamineFos-Related Antigen 1JNK Mitogen-Activated Protein KinasesmirdametinibNaphthyridinesNF-kappa BPhenazinesProto-Oncogene Proteins c-fossilmitasertibTumor Suppressor Protein p53CK2 inhibitorCX-4945head and neck cancer.MEK inhibitorPD-0325901

Identifiers

PMID25798061
PMCPMC4366640
OpenAlexW2163573273

What OpenQuestion holds

Textmetadata
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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.