Evidence map›Paper›PMID 22927676›Full record

ArticleJournal of biomolecular screening2012

A 1536-well quantitative high-throughput screen to identify compounds targeting cancer stem cells.

Lesley A Mathews, Jonathan M Keller, Bonnie L Goodwin, Rajarshi Guha, Paul Shinn, Rebecca Mull, Craig J Thomas, Rachel L de Kluyver, Thomas J Sayers, Marc Ferrer

Open access · hybridAbstract read
In one paragraph

Article in Journal of biomolecular screening, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
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  5. An OpenData portal to share COVID-19 drug repurposing data in real time.bioRxiv : the preprint server for biology · 2020
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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

10 authors at 4 institutions in 2 countries.

Lesley A MathewsDivision of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD 20850, USA. mathewsla@mail.nih.gov
Jonathan M Keller
Bonnie L Goodwin
Rajarshi Guha
Paul Shinn
Rebecca Mull
Craig J Thomas
Rachel L de Kluyver
Thomas J Sayers
Marc Ferrer
National Center for Advancing Translational Sciences · USNational Institutes of Health · USNorthern Sydney Local Health District · AUScience Applications International Corporation (United States) · US

Funding

NIH Chemical Genomics CenterZIBHG200319 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI AUSTIN, CHRISTOPHER P · 2010 to 2011
$55.9M
NIH Chemical Genomics CenterZIBTR000004 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI MCKEW, JOHN · 2012 to 2014
$52.3M
Mechanisms of Immune-mediated Tumor Cell DestructionZIABC010012 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SAYERS, THOMAS · 2009 to 2018
$3.3M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIB HG200319NCI NIH HHS HHSN261200800001ENIMH NIH HHS U54 MH084681
6 · The paper itself

Abstract

Tumor cell subpopulations called cancer stem cells (CSCs) or tumor-initiating cells (TICs) have self-renewal potential and are thought to drive metastasis and tumor formation. Data suggest that these cells are resistant to current chemotherapy and radiation therapy treatments, leading to cancer recurrence. Therefore, finding new drugs and/or drug combinations that cause death of both the differentiated tumor cells as well as CSC populations is a critical unmet medical need. Here, we describe how cancer-derived CSCs are generated from cancer cell lines using stem cell growth media and nonadherent conditions in quantities that enable high-throughput screening (HTS). A cell growth assay in a 1536-well microplate format was developed with these CSCs and used to screen a focused collection of oncology drugs and clinical candidates to find compounds that are cytotoxic against these highly aggressive cells. A hit selection process that included potency and efficacy measurements during the primary screen allowed us to efficiently identify compounds with potent cytotoxic effects against spheroid-derived CSCs. Overall, this research demonstrates one of the first miniaturized HTS assays using CSCs. The procedures described here should enable further testing of the effect of compounds on CSCs and help determine which pathways need to be targeted to kill them.

Indexed as

AnimalsAntineoplastic AgentsCell Culture TechniquesCell Line, TumorCell ProliferationDrug DiscoveryDrug Evaluation, PreclinicalHigh-Throughput Screening AssaysHomeodomain ProteinsHumansMaleMiceNanog Homeobox ProteinNeoplasmsNeoplastic Stem CellsSmall Molecule LibrariesAntineoplastic AgentsHomeodomain ProteinsNanog Homeobox ProteinNanog protein, mouseSmall Molecule Libraries

Identifiers

PMID22927676
PMCPMC6993186
OpenAlexW2007253892

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.