Evidence map›Paper›PMID 33907275›Full record

ArticleScientific reports2021

The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers.

Avisek Majumder, Manbir Sandhu, Debarko Banerji, Veronica Steri, Adam Olshen, Mark M Moasser

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.1field-weighted citation impact, top 4% 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

36 citing papers in PubMed, 53 citations in OpenAlex.

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  19. The Role of Beclin 1 and HER2 in Colorectal Carcinoma; An Immunohistochemical Study.Asian Pacific journal of cancer prevention : APJCP · 2024
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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

6 authors at 3 institutions in 1 country.

Avisek MajumderDepartment of Medicine, University of California, San Francisco, Box 3111, San Francisco, CA, 94143, USA.
Manbir SandhuDepartment of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105-3678, USA.
Debarko BanerjiGenentech, Inc, 1 DNA Way, South San Francisco, CA, 94080-4990, USA.
Veronica SteriHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 94143, USA.
Adam OlshenHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 94143, USA.
Mark M MoasserDepartment of Medicine, University of California, San Francisco, Box 3111, San Francisco, CA, 94143, USA. mark.moasser@ucsf.edu.
University of California, San Francisco · USSt. Jude Children's Research Hospital · USUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Leigh Clarke · 1999 to 2026
$209.7M
Understanding resistance to HER family tyrosine kinase inhibitorsR01CA122216 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MOASSER, MARK M · 2007 to 2017
$3.0M
NCI NIH HHS P30 CA082103NCI NIH HHS R01 CA122216NIH HHS CA122216NIH HHS P30CA082103
6 · The paper itself

Abstract

HER2 and HER3 play key driving functions in the pathophysiology of HER2-amplified breast cancers, but this function is less well characterized in other cancers driven by HER2 amplification. This study aimed to explore the role of HER2 and HER3 signaling in other types of HER2-amplified cancer. The expression and signaling activity of HER2, HER3, and downstream pathway proteins were studied in cell panels representing HER2-amplified cancers of the breast, bladder, colon and rectal, stomach, esophagus, lung, tongue, and endometrium along with controls lacking HER2 amplification. We report that HER2-amplified cancers are addicted to HER2 across different cancer types and the depth of addiction is best linked with the expression level of HER2, but not with HER3 expression. We report that the expression and constitutive phosphorylation of HER3 are ubiquitous in HER2-amplified breast cancer cell lines, but much more variable in HER2-amplified cancer cells from other tissues. We observed the lapatinib-induced compensatory upregulation of HER3 signaling in many types of HER2-amplified cancers, although with much variability. We find that HER3 expression is essential for in vivo tumorigenic growth in some HER2-amplified tumors but not others. Importantly HER3 expression level does not correlate well with its functional importance. More biomarkers will be needed to guide the optimal use of HER3 inhibitors in HER2-amplified cancers from non-breast origin. Unlike oncogenes activated through mutational events, the activation of HER2 through overexpression represents a gradient of activities and depth of addiction and the response to inhibitors follows a similar gradient.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorErb-b2 Receptor Tyrosine KinasesFemaleGene Expression Regulation, NeoplasticHumansLapatinibMiceMice, Inbred NODNeoplasmsPhosphorylationReceptor, ErbB-3Xenograft Model Antitumor AssaysERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanLapatinibReceptor, ErbB-3

Identifiers

PMID33907275
PMCPMC8079373
OpenAlexW3157258448

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.