Evidence map›Paper›PMID 24699253›Full record

ArticlePloS one2014

High-throughput screening for the identification of new therapeutic options for metastatic pheochromocytoma and paraganglioma.

Alessio Giubellino, Uma Shankavaram, Petra Bullova, Jan Schovanek, Yaqin Zhang, Min Shen, Nikita Patel, Abdel Elkahloun, Min-Jung Lee, Jane Trepel and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

12 authors at 5 institutions in 3 countries.

Alessio GiubellinoProgram in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH, Bethesda, Maryland, United States of America.
Uma ShankavaramRadiation Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Petra BullovaProgram in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH, Bethesda, Maryland, United States of America; Department of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Jan SchovanekProgram in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH, Bethesda, Maryland, United States of America; Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, University Hospital of Olomouc, Czech Republic.
Yaqin ZhangNational Center for Advancing Translational Sciences, NIH, Rockville, Maryland, United States of America.
Min ShenNational Center for Advancing Translational Sciences, NIH, Rockville, Maryland, United States of America.
Nikita PatelProgram in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH, Bethesda, Maryland, United States of America.
Abdel ElkahlounNational Human Genome Research Institute, NIH, Bethesda, Maryland, United States of America.
Min-Jung LeeMedical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Jane TrepelMedical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Marc FerrerNational Center for Advancing Translational Sciences, NIH, Rockville, Maryland, United States of America.
Karel PacakProgram in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH, Bethesda, Maryland, United States of America.
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Cancer Institute · USNational Center for Advancing Translational Sciences · USNational Human Genome Research Institute · USUniversity Hospital Olomouc · CZ

Funding

NIH Chemical Genomics CenterZIBTR000004 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI MCKEW, JOHN · 2012 to 2014
$52.3M
Diagnosis, Pathophysiology And Molecular Biology of Pheochromocytoma and ParagangliomaZIAHD008735 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PACAK, KAREL · 2009 to 2024
$28.4M
Signal Transduction Events and the Regulation of Cell GrowthZICSC006743 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI TREPEL, JANE B · 2009 to 2023
$13.8M
NHGRI/DIR Microarray CoreZICHG200365 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI ELKAHLOUN, ABDEL · 2011 to 2025
$9.0M
Intramural NIH HHS
6 · The paper itself

Abstract

Drug repurposing or repositioning is an important part of drug discovery that has been growing in the last few years for the development of therapeutic options in oncology. We applied this paradigm in a screening of a library of about 3,800 compounds (including FDA-approved drugs and pharmacologically active compounds) employing a model of metastatic pheochromocytoma, the most common tumor of the adrenal medulla in children and adults. The collection of approved drugs was screened in quantitative mode, testing the compounds in compound-titration series (dose-response curves). Analysis of the dose-response screening data facilitated the selection of 50 molecules with potential bioactivity in pheochromocytoma cells. These drugs were classified based on molecular/cellular targets and signaling pathways affected, and selected drugs were further validated in a proliferation assay and by flow cytometric cell death analysis. Using meta-analysis information from molecular targets of the top drugs identified by our screening with gene expression data from human and murine microarrays, we identified potential drugs to be used as single drugs or in combination. An example of a combination with a synergistic effect is presented. Our study exemplifies a promising model to identify potential drugs from a group of clinically approved compounds that can more rapidly be implemented into clinical trials in patients with metastatic pheochromocytoma or paraganglioma.

Indexed as

Drug DiscoveryDrug RepositioningHigh-Throughput Screening AssaysAdrenal Gland NeoplasmsAdultAnimalsAntineoplastic AgentsBiomarkers, TumorBlotting, WesternCell ProliferationFlow CytometryGene Expression ProfilingHumansMiceOligonucleotide Array Sequence AnalysisParagangliomaAntineoplastic AgentsBiomarkers, TumorRNA, Messenger

Identifiers

PMID24699253
PMCPMC3974653
OpenAlexW2047296992

What OpenQuestion holds

Textmetadata
LicenceCC0
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.