Evidence map›Paper›PMID 26138066›Full record

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

Increased Expression of HER2, HER3, and HER2:HER3 Heterodimers in HPV-Positive HNSCC Using a Novel Proximity-Based Assay: Implications for Targeted Therapies.

Netanya I Pollock, Lin Wang, Gerald Wallweber, William E Gooding, Weidong Huang, Ahmed Chenna, John Winslow, Malabika Sen, Kara A DeGrave, Hua Li and 2 more

Open access · bronzeAbstract read
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 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.7field-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

31 citing papers in PubMed, 61 citations in OpenAlex.

  1. Trial
  2. Assessment of EGFR and HER2 expression in penile cancer as potential therapeutic targets.Virchows Archiv : an international journal of pathology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Netanya I PollockUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Lin WangUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Gerald WallweberMonogram Biosciences/Labcorp, Inc., South San Francisco, California.
William E GoodingUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Weidong HuangMonogram Biosciences/Labcorp, Inc., South San Francisco, California.
Ahmed ChennaMonogram Biosciences/Labcorp, Inc., South San Francisco, California.
John WinslowMonogram Biosciences/Labcorp, Inc., South San Francisco, California.
Malabika SenUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Kara A DeGraveUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Hua LiUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Yan ZengUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Jennifer R GrandisUniversity of California San Francisco, San Francisco, California. Jennifer.grandis@ucsf.edu.
University of California, San Francisco · US

Funding

WILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2004 to 2026
$49.6M
PI3K Pathway Mutations in Head and Neck CancerR01DE023685 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRANDIS, JENNIFER RUBIN, JOHNSON, DANIEL E · 2014 to 2023
$5.1M
NCI NIH HHS P50 CA097190NCI NIH HHS P50CA97190NIDCR NIH HHS R01 DE023685NIDCR NIH HHS R01DE023685
6 · The paper itself

Abstract

purposeIn other cancer types, HPV infection has been reported to coincide with overexpression of HER2 (ERBB2) and HER3 (ERBB3); however, the association between HER2 or HER3 expression and dimer formation in HNSCC has not been reported. Overexpression of HER2 and HER3 may contribute to resistance to EGFR inhibitors, including cetuximab, although the contribution of HPV in modulating cetuximab response remains unknown. Determination of heterodimerization of HER receptors is challenging and has not been reported in HNSCC. The present study aimed to determine the expression of HER proteins in HPV(+) versus HPV(-) HNSCC tumors using a proximity-based protein expression assay (VeraTag), and to determine the efficacy of HER-targeting agents in HPV(+) and HPV(-) HNSCC cell lines. EXPERIMENTAL

designExpression of total HER1, HER2, and HER3, p95HER2, p-HER3, HER1:HER1 homodimers, HER2:HER3 heterodimers, and the HER3-PI3K complex in 88 HNSCC was determined using VeraTag, including 33 baseline tumors from individuals treated in a trial including cetuximab. Inhibition of cell growth and protein activation with cetuximab and afatinib was compared in HPV(+) and HPV(-) cetuximab-resistant cell lines.

resultsExpression of total HER2, total HER3, HER2:HER3 heterodimers, and the HER3:PI3K complex were significantly elevated in HPV(+) HNSCC. Total EGFR was significantly increased in HPV(-) HNSCC where VeraTag assay results correlated with IHC. Afatinib significantly inhibited cell growth when compared with cetuximab in the HPV(+) and HPV(-) cetuximab-resistant HNSCC cell lines.

conclusionsThese findings suggest that agents targeting multiple HER proteins may be effective in the setting of HPV(+) HNSCC and/or cetuximab resistance.

Indexed as

AdultAgedAged, 80 and overAntineoplastic AgentsCarcinoma, Squamous CellCell Line, TumorCetuximabDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleHead and Neck NeoplasmsHumansMaleMiddle AgedPapillomaviridaeAntineoplastic AgentsCetuximabERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanErbB ReceptorsPhosphatidylinositol 3-KinasesReceptor, ErbB-3

Identifiers

PMID26138066
PMCPMC4609280
OpenAlexW1961186603

What OpenQuestion holds

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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.