Evidence map›Paper›PMID 24952873›Full record

ArticleOncotarget2014

ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer.

Katharina Feldinger, Daniele Generali, Gabriela Kramer-Marek, Merel Gijsen, T B Ng, Jack Ho Wong, Carla Strina, Mariarosa Cappelletti, Daniele Andreis, Ji-Liang Li and 8 more

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

Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

51 citing papers in PubMed, 88 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 4 countries.

Katharina FeldingerHuman Epidermal Growth Factor Group, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Daniele GeneraliU.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Instituti Ospitalieri di Cremona, Cremona, Italy.
Gabriela Kramer-MarekNational Institutes of Health, Radiation Oncology Branch, Bethesda MD, US. Institute of Cancer Research, Division of Radiotherapy and Imaging, Belmont, Sutton, Surrey, UK (New address).
Merel GijsenHuman Epidermal Growth Factor Group, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
T B NgSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Tai Po Road, Sha Tin, Hong Kong.
Jack Ho WongSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Tai Po Road, Sha Tin, Hong Kong.
Carla StrinaU.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Instituti Ospitalieri di Cremona, Cremona, Italy.
Mariarosa CappellettiU.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Instituti Ospitalieri di Cremona, Cremona, Italy.
Daniele AndreisU.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Instituti Ospitalieri di Cremona, Cremona, Italy.
Ji-Liang LiGrowth Factor Group, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Esther BridgesGrowth Factor Group, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Helen TurleyGrowth Factor Group, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Russell LeekGrowth Factor Group, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Ioannis RoxanisDepartment of Cellular Pathology, Oxford University Hospitals and Oxford Biomedical Research Centre, Oxford, UK.
Jacek CapalaNational Institutes of Health, Radiation Oncology Branch, Bethesda MD, US.
Gillian MurphyCancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.
Adrian L HarrisGrowth Factor Group, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Anthony KongHuman Epidermal Growth Factor Group, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
University of Oxford · GBIstituti Ospitalieri di Cremona · ITJohn Radcliffe Hospital · GBChinese University of Hong Kong · CNNational Institutes of Health · USCancer Research UK · GBOxford BioMedica (United Kingdom) · GB

Funding

Cancer Research UK 11359Cancer Research UK 16464
6 · The paper itself

Abstract

Trastuzumab prolongs survival in HER2 positive breast cancer patients. However, resistance remains a challenge. We have previously shown that ADAM17 plays a key role in maintaining HER2 phosphorylation during trastuzumab treatment. Beside ADAM17, ADAM10 is the other well characterized ADAM protease responsible for HER ligand shedding. Therefore, we studied the role of ADAM10 in relation to trastuzumab treatment and resistance in HER2 positive breast cancer. ADAM10 expression was assessed in HER2 positive breast cancer cell lines and xenograft mice treated with trastuzumab. Trastuzumab treatment increased ADAM10 levels in HER2 positive breast cancer cells (p ≤ 0.001 in BT474; p ≤ 0.01 in SKBR3) and in vivo (p ≤ 0.0001) compared to control, correlating with a decrease in PKB phosphorylation. ADAM10 inhibition or knockdown enhanced trastuzumab response in naïve and trastuzumab resistant breast cancer cells. Trastuzumab monotherapy upregulated ADAM10 (p ≤ 0.05); and higher pre-treatment ADAM10 levels correlated with decreased clinical response (p ≤ 0.05) at day 21 in HER2 positive breast cancer patients undergoing a trastuzumab treatment window study. Higher ADAM10 levels correlated with poorer relapse-free survival (p ≤ 0.01) in a cohort of HER2 positive breast cancer patients. Our studies implicate a role of ADAM10 in acquired resistance to trastuzumab and establish ADAM10 as a therapeutic target and a potential biomarker for HER2 positive breast cancer patients.

Indexed as

ADAM10 ProteinADAM ProteinsAmyloid Precursor Protein SecretasesAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell ProliferationDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleGene Knockdown TechniquesHumansMembrane ProteinsMiceADAM10 ProteinADAM10 protein, humanADAM ProteinsAmyloid Precursor Protein SecretasesAntibodies, Monoclonal, HumanizedAntineoplastic AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesMembrane ProteinsTrastuzumab

Identifiers

PMID24952873
PMCPMC4196152
OpenAlexW1506037014

What OpenQuestion holds

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Registered trials

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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.