Evidence map›Paper›PMID 30777098›Full record

ArticleBreast cancer research : BCR2019

MEDI3039, a novel highly potent tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2 agonist, causes regression of orthotopic tumors and inhibits outgrowth of metastatic triple-negative breast cancer.

Yoshimi Endo Greer, Samuel F Gilbert, Brunilde Gril, Rajesh Narwal, Danielle L Peacock Brooks, David A Tice, Patricia S Steeg, Stanley Lipkowitz

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

Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
6.7field-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

35 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
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  3. Advances in the study of death receptor 5.Frontiers in pharmacology · 2025
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  8. Assessment of the sensitivity ofNMR in biomedicine · 2023
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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

8 authors at 2 institutions in 1 country.

Yoshimi Endo GreerWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 4B54, Bethesda, MD, 20892-1361, USA.
Samuel F GilbertWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 4B54, Bethesda, MD, 20892-1361, USA.
Brunilde GrilWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 4B54, Bethesda, MD, 20892-1361, USA.
Rajesh NarwalMedImmune, LLC, Gaithersburg, MD, USA.
Danielle L Peacock BrooksWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 4B54, Bethesda, MD, 20892-1361, USA.
David A TiceMedImmune, LLC, Gaithersburg, MD, USA.
Patricia S SteegWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 4B54, Bethesda, MD, 20892-1361, USA.
Stanley LipkowitzWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 4B54, Bethesda, MD, 20892-1361, USA. lipkowis@mail.nih.gov.
Center for Cancer Research · USNational Cancer Institute · US

Funding

TRAIL-induced Cell Death in Breast Cancer CellsZIASC007263 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI LIPKOWITZ, STANLEY · 2009 to 2025
$11.8M
Intramural NIH HHS ZIA SC007263
6 · The paper itself

Abstract

backgroundTNF-related apoptosis-inducing ligand (TRAIL) receptor agonists are attractive anti-tumor agents because of their capability to induce apoptosis in cancer cells by activating death receptors (DR) 4 and 5 with little toxicity against normal cells. Despite an attractive mechanism of action, previous clinical efforts to use TRAIL receptor agonists have been unsuccessful. In this study, we examined MEDI3039, a highly potent multivalent DR5 agonist, in breast cancer cell lines and in vivo models.

methodsAs in vitro model systems, we used 19 breast cancer cell lines that are categorized into four subtypes: ER+, HER2 amplified, basal A (triple-negative breast cancer) TNBC, and basal B TNBC. Cell viability was analyzed by MTS and RealTime live/dead assays. As in vivo model systems, MDA-MB231T orthotopic primary tumor growth in the mammary fat pad (MFP) and two experimental lung metastasis models were used. The effect of MEDI3039 on MFP tumors was assessed with immunohistochemical analysis. Lung metastases were analyzed with Bouin's and H&E staining.

resultsMEDI3039 killed multiple breast cancer cell lines, but the sensitivity varied among different subtypes. Sensitivity was basal B TNBC >> basal A TNBC > HER2 amplified > ER+ (average IC

conclusionMEDI3039 is a potent DR5 agonist in breast cancer cells in vitro and in vivo and has potential as a cancer drug in breast cancer patients, especially those with basal B TNBC.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationFemaleHumansInhibitory Concentration 50Lung NeoplasmsMiceMice, NudeReceptors, TNF-Related Apoptosis-Inducing LigandSurvival AnalysisTreatment OutcomeTriple Negative Breast NeoplasmsXenograft Model Antitumor AssaysAntineoplastic AgentsReceptors, TNF-Related Apoptosis-Inducing LigandTNFRSF10B protein, humanAgonistApoptosisBreast cancerDeath receptorTRAILTriple-negative breast cancer

Identifiers

PMID30777098
PMCPMC6380056
OpenAlexW2922527045

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.