Evidence map›Paper›PMID 27004400›Full record

ArticleOncotarget2016

MAPK1E322K mutation increases head and neck squamous cell carcinoma sensitivity to erlotinib through enhanced secretion of amphiregulin.

Yihui Wen, Hua Li, Yan Zeng, Weiping Wen, Kelsey P Pendleton, Vivian W Y Lui, Ann Marie Egloff, Jennifer R Grandis

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 29% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Erlotinib sensitivity ofNPJ genomic medicine · 2020
    Article
  6. Article
  7. EGFR-targeted therapies in the post-genomic era.Cancer metastasis reviews · 2017
    Review
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

8 authors at 5 institutions in 3 countries.

Yihui WenDepartment of Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
Hua LiDepartment of Otolaryngology Head and Neck Surgery, University of California at San Francisco, San Francisco, California, USA.
Yan ZengDepartment of Otolaryngology Head and Neck Surgery, University of California at San Francisco, San Francisco, California, USA.
Weiping WenDepartment of Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
Kelsey P PendletonDepartment of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Vivian W Y LuiDepartment of Pharmacology and Pharmacy, School of Biomedical Sciences, Li-Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR.
Ann Marie EgloffDepartment of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jennifer R GrandisDepartment of Otolaryngology Head and Neck Surgery, University of California at San Francisco, San Francisco, California, USA.
University of Pittsburgh · USUniversity of California, San Francisco · USSouthern California Clinical and Translational Science Institute · USThe First Affiliated Hospital, Sun Yat-sen University · CNUniversity of Hong Kong · HK

Funding

WILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2004 to 2026
$49.6M
Genomic and Proteomic Biomarkers for Head and Neck Cancer Risk and PrognosisK07CA137140 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI EGLOFF, ANN MARIE · 2009 to 2013
$519k
NCI NIH HHS K07 CA137140NCI NIH HHS P50 CA097190
6 · The paper itself

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have not been effective in unselected head and neck squamous cell carcinoma (HNSCC) populations. We previously reported an exceptional response to a brief course of erlotinib in a patient with advanced HNSCC whose tumor harbored a MAPK1E322K somatic mutation. MAPK1E322Kwas associated with increased p-EGFR, increased EGFR downstream signaling and increased sensitivity to erlotinib. In this study, we investigated the mechanism of MAPK1E322K-mediated EGFR activation in the context of erlotinib sensitivity. We demonstrated increased AREG secretion in HNSCC cell lines harboring endogenous or exogenous MAPK1E322K compared to wild type MAPK1. We found inhibition or knockdown of MAPK1 with siRNA resulted in reduced secretion of AREG and decreased sensitivity to erlotinib in the setting of MAPK1E322K. MAPK1E322K was associated with increased AREG secretion leading to an autocrine feedback loop involving AREG, EGFR and downstream signaling. Knockdown of AREG in HNSCC cells harboring MAPK1E322K abrogated EGFR signaling and decreased sensitivity to erlotinib in vitro and in vivo. These cumulative findings implicate increased AREG secretion and EGFR activation as contributing to increased erlotinib sensitivity in MAPK1E322K HNSCC.

Indexed as

MutationAmphiregulinAnimalsAntineoplastic AgentsApoptosisBiomarkers, TumorCarcinoma, Squamous CellCell ProliferationErlotinib HydrochlorideFemaleHead and Neck NeoplasmsHumansMiceMice, NudeMitogen-Activated Protein Kinase 1Signal TransductionAmphiregulinAntineoplastic AgentsBiomarkers, TumorErlotinib HydrochlorideMAPK1 protein, humanMitogen-Activated Protein Kinase 1amphiregulinERK2head and neck cancerMAPK1mutation

Identifiers

PMID27004400
PMCPMC5029627
OpenAlexW2345560211

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.