Evidence map›Paper›PMID 37716943›Full record

ArticleCancer cell international2023

HER3 functions as an effective therapeutic target in triple negative breast cancer to potentiate the antitumor activity of gefitinib and paclitaxel.

Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D Thor, Bolin Liu

Open access · goldAbstract read
In one paragraph

Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed, 13 citations in OpenAlex.

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  10. Targeting low-risk triple-negative breast cancer: a review on de-escalation strategies for a new era.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025
    Review
  11. 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

7 authors at 4 institutions in 2 countries.

Hui Lyu *Departments of Interdisciplinary Oncology and Genetics, Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University (LSU) Health Sciences Center, 1700 Tulane Ave, New Orleans, LA, 70112, USA.
Fei Shen *Jiangsu Institute of Hematology, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Sanbao RuanDepartments of Interdisciplinary Oncology and Genetics, Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University (LSU) Health Sciences Center, 1700 Tulane Ave, New Orleans, LA, 70112, USA.
Congcong TanDepartments of Interdisciplinary Oncology and Genetics, Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University (LSU) Health Sciences Center, 1700 Tulane Ave, New Orleans, LA, 70112, USA.
Jundong ZhouSuzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, China.
Ann D ThorDepartment of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Bolin LiuDepartments of Interdisciplinary Oncology and Genetics, Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University (LSU) Health Sciences Center, 1700 Tulane Ave, New Orleans, LA, 70112, USA. bliu2@lsuhsc.edu.
Louisiana State University Health Sciences Center New Orleans · USNanjing Medical University · CNSoochow University · CNUniversity of Colorado Anschutz Medical Campus · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTriple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease.

methodsImmunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. Specific shRNA was used to knockdown HER3 expression. IncuCyte system was utilized to monitor cell growth and migration. LIVE/DEAD Cell Imaging was to detect live and dead cells. HER3 recognition by our anti-HER3 monoclonal antibody (mAb) 4A7 was verified by ELISA, flow cytometry, and co-immunoprecipitation assays. Orthotopic tumor models were established in nude mice to determine the capability of TNBC cells forming tumors and to test if our mAb 4A7 could potentiate the antitumor activity of paclitaxel in vivo.

resultsElevated expression of HER3 was observed in approximately half of the TNBC specimens and cell lines tested. Analyses of TCGA databases found that the TNBC patients with high HER3 mRNA expression in the tumors showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with low HER3 expression. Specific knockdown of HER3 markedly inhibited TNBC cell proliferation and mammosphere formation in vitro and tumor growth in vivo. Our mAb 4A7 abrogated heregulin (a ligand for HER3), but not SDF-1 (a ligand for CXCR4)-induced enhancement of TNBC cell migration. Combinations of 4A7 and the EGFR-tyrosine kinase inhibitor (TKI) gefitinib dramatically decreased the levels of phosphorylated HER3, EGFR, Akt, and ERK1/2 in TNBC cells and potently induced growth inhibition and cell death. Moreover, 4A7 in combination with paclitaxel exerted significant antitumor activity against TNBC in vitro and in vivo.

conclusionsOur data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of gefitinib or paclitaxel in TNBC.

Indexed as

Blocking antibodyEGFRHER3PaclitaxelTargeted therapyTNBC

Identifiers

PMID37716943
PMCPMC10504712
OpenAlexW4386802413

What OpenQuestion holds

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LicenceCC BY
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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.