Evidence map›Paper›PMID 30949858›Full record

ArticleThe AAPS journal2019

HER3-Targeted Affibodies with Optimized Formats Reduce Ovarian Cancer Progression in a Mouse Xenograft Model.

John S Schardt, Madeleine Noonan-Shueh, Jinan M Oubaid, Alex Eli Pottash, Sonya C Williams, Arif Hussain, Rena G Lapidus, Stanley Lipkowitz, Steven M Jay

Open access · greenAbstract read
In one paragraph

Article in The AAPS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022
    Review
  4. Article
  5. 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

9 authors at 3 institutions in 1 country.

John S SchardtFischell Department of Bioengineering, University of Maryland, 3116 A. James Clark Hall, College Park, Maryland, 20742, USA.
Madeleine Noonan-ShuehFischell Department of Bioengineering, University of Maryland, 3116 A. James Clark Hall, College Park, Maryland, 20742, USA.
Jinan M OubaidFischell Department of Bioengineering, University of Maryland, 3116 A. James Clark Hall, College Park, Maryland, 20742, USA.
Alex Eli PottashFischell Department of Bioengineering, University of Maryland, 3116 A. James Clark Hall, College Park, Maryland, 20742, USA.
Sonya C WilliamsFischell Department of Bioengineering, University of Maryland, 3116 A. James Clark Hall, College Park, Maryland, 20742, USA.
Arif HussainBaltimore VA Medical Center, Baltimore, Maryland, United States of America.
Rena G LapidusMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Stanley LipkowitzWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Steven M JayFischell Department of Bioengineering, University of Maryland, 3116 A. James Clark Hall, College Park, Maryland, 20742, USA. smjay@umd.edu.ORCID 0000-0002-3827-5988
University of Maryland, College Park · USUniversity of Maryland, Baltimore · USNational Institutes of Health · US

Funding

Cbl Proteins as Regulators of Tyrosine Kinase SignalingZIABC010977 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LIPKOWITZ, STANLEY · 2009 to 2025
$13.4M
Training in Host-pathogens interactionsT32AI089621 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI LEE, VINCENT T, MCIVER, KEVIN S. · 2010 to 2025
$2.1M
Engineering NRG Signaling For Therapeutic Vascularization In Diabetic WoundsR00HL112905 · NHLBI · UNIV OF MARYLAND, COLLEGE PARK · PI JAY, STEVEN MICHAEL · 2013 to 2015
$730k
Optimization of Multi-Modal Therapies in Pre-clinical models of Prostate CancerI01BX000545 · VA · BALTIMORE VA MEDICAL CENTER · PI HUSSAIN, ARIF · 2009 to 2021
–
BLRD VA I01 BX000545NHLBI NIH HHS R00 HL112905NIAID NIH HHS T32 AI089621
6 · The paper itself

Abstract

Expression of the receptor tyrosine kinase HER3 is negatively correlated with survival in ovarian cancer, and HER3 overexpression is associated with cancer progression and therapeutic resistance. Thus, improvements in HER3-targeted therapy could lead to significant clinical impact for ovarian cancer patients. Previous work from our group established multivalency as a potential strategy to improve the therapeutic efficacy of HER3-targeted ligands, including affibodies. Others have established HER3 affibodies as viable and potentially superior alternatives to monoclonal antibodies for cancer therapy. Here, bivalent HER3 affibodies were engineered for optimized production, specificity, and function as evaluated in an ovarian cancer xenograft model. Enhanced inhibition of HER3-mediated signaling and increased HER3 downregulation associated with multivalency could be achieved with a simplified construct, potentially increasing translational potential. Additionally, functional effects of affibodies due to multivalency were found to be specific to HER3 targeting, suggesting a unique molecular mechanism. Further, HER3 affibodies demonstrated efficacy in ovarian cancer xenograft mouse models, both as single agents and in combination with carboplatin. Overall, these results reinforce the potential of HER3-targeted affibodies for cancer therapy and establish treatment of ovarian cancer as an application where multivalent HER3 ligands may be useful. Further, this work introduces the potential of HER3 affibodies to be utilized as part of clinically relevant combination therapies (e.g., with carboplatin).

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCell Line, TumorDrug Resistance, NeoplasmFemaleHalf-LifeHumansMiceOvarian NeoplasmsProtein Kinase InhibitorsReceptor, ErbB-3Recombinant Fusion ProteinsTreatment OutcomeXenograft Model Antitumor AssaysCarboplatinERBB3 protein, humanProtein Kinase InhibitorsReceptor, ErbB-3Recombinant Fusion ProteinsaffibodycarboplatinErbB3HER3ovarian cancer

Identifiers

PMID30949858
PMCPMC7261481
OpenAlexW2932157088

What OpenQuestion holds

Textmetadata
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.