Evidence map›Paper›PMID 32161105›Full record

ArticleScience translational medicine2020

Targeting MYCN-expressing triple-negative breast cancer with BET and MEK inhibitors.

Johanna M Schafer, Brian D Lehmann, Paula I Gonzalez-Ericsson, Clayton B Marshall, J Scott Beeler, Lindsay N Redman, Hailing Jin, Violeta Sanchez, Matthew C Stubbs, Peggy Scherle and 12 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

49 citing papers in PubMed, 72 citations in OpenAlex.

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  18. Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
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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

22 authors at 4 institutions in 1 country.

Johanna M SchaferDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0001-7834-5621
Brian D LehmannDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0003-0407-5248
Paula I Gonzalez-EricssonVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0002-6292-6963
Clayton B MarshallDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0002-9974-1604
J Scott BeelerDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0002-1829-1972
Lindsay N RedmanDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0003-2769-3196
Hailing JinVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0002-7260-8723
Violeta SanchezVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0001-6639-9024
Matthew C StubbsIncyte Corporation, Wilmington, DE 19803, USA.ORCID 0000-0003-3771-7083
Peggy ScherlePrelude Therapeutics, Wilmington, DE 19803, USA.ORCID 0000-0003-0783-6815
Kimberly N JohnsonVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Quanhu ShengDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0001-8951-9295
Joseph T RolandSection of Surgical Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0001-9977-0520
Joshua A BauerDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0002-8019-900X
Yu ShyrDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0003-2086-9670
Bapsi ChakravarthyVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0003-2824-2514
Bret C MobleyDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0002-8138-5330
Scott W HiebertDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
Justin M BalkoDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0002-4263-5974
Melinda E SandersVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Phillip C C LiuKymera Therapeutics, Cambridge, MA 02139, USA.
Jennifer A PietenpolDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA. j.pietenpol@vumc.org.ORCID 0000-0001-6268-6798
Vanderbilt University Medical Center · USVanderbilt University · USAkebia Therapeutics (United States) · USIncyte (United States) · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7M
Cancer Pharmacologist and HTS ScientistR50CA211206 · NCI · VANDERBILT UNIVERSITY · PI Joshua A. Bauer · 2016 to 2026
$1.8M
Functional genomics approach to evaluate mechanisms of mutant p53 gain-of-function phenotypesF31CA247356 · NCI · VANDERBILT UNIVERSITY · PI REDMAN, LINDSAY · 2019 to 2021
$70k
NCI NIH HHS F31 CA247356NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA098131NCI NIH HHS R50 CA211206
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that does not respond to endocrine therapy or human epidermal growth factor receptor 2 (HER2)-targeted therapies. Individuals with TNBC experience higher rates of relapse and shorter overall survival compared to patients with receptor-positive breast cancer subtypes. Preclinical discoveries are needed to identify, develop, and advance new drug targets to improve outcomes for patients with TNBC. Here, we report that MYCN, an oncogene typically overexpressed in tumors of the nervous system or with neuroendocrine features, is heterogeneously expressed within a substantial fraction of primary and recurrent TNBC and is expressed in an even higher fraction of TNBCs that do not display a pathological complete response after neoadjuvant chemotherapy. We performed high-throughput chemical screens on TNBC cell lines with varying amounts of MYCN expression and determined that cells with higher expression of MYCN were more sensitive to bromodomain and extraterminal motif (BET) inhibitors. Combined BET and MEK inhibition resulted in a synergistic decrease in viability, both in vitro and in vivo, using cell lines and patient-derived xenograft (PDX) models. Our preclinical data provide a rationale to advance a combination of BET and MEK inhibitors to clinical investigation for patients with advanced MYCN-expressing TNBC.

Indexed as

Triple Negative Breast NeoplasmsAnimalsBromodomain Containing ProteinsCell Line, TumorHumansMitogen-Activated Protein Kinase KinasesNeoplasm Recurrence, LocalN-Myc Proto-Oncogene ProteinProteinsXenograft Model Antitumor Assaysbromodomain and extra-terminal domain protein, humanBromodomain Containing ProteinsMitogen-Activated Protein Kinase KinasesMYCN protein, humanN-Myc Proto-Oncogene ProteinProteins

Identifiers

PMID32161105
PMCPMC7427123
OpenAlexW3011851683

What OpenQuestion holds

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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.