Evidence map›Paper›PMID 21817115›Full record

ArticleMolecular cancer therapeutics2011

Dual-fluorescence isogenic high-content screening for MUC16/CA125 selective agents.

Thapi D Rao, Nestor Rosales, David R Spriggs

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.1field-weighted citation impact, top 41% 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

6 citing papers in PubMed, 12 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

3 authors at 2 institutions in 1 country.

Thapi D RaoLaboratory of Clinical Pharmacology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Nestor Rosales
David R Spriggs
Memorial Hospital · USMemorial Sloan Kettering Cancer Center · US

Funding

The Molecular Genetics of MUC16P01CA052477 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SOSLOW, ROBERT A · 1991 to 2009
$15.7M
NEW INVESTIGATOR TRAINING IN DRUG DEVELOPMENTK24CA087933 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SPRIGGS, DAVID R · 2000 to 2010
$1.3M
NCI NIH HHS K24 CA087933NCI NIH HHS P01 CA052477NCI NIH HHS P01-CA52477-17
6 · The paper itself

Abstract

Most of the currently used cancer chemotherapies are based on compounds that inhibit general cellular mechanisms, such as DNA replication or tubulin function, and lack specificity in relation to features of the cancer cell. Recent advances in genomic studies have increased our knowledge of tumor cell biology, and a panoply of new targets have been postulated. This has provided an opportunity to develop and validate drugs that specifically target cancer cells through their unique genetic characteristics. Identification of MUC16/CA125 both as a marker and a driver of transformation led us to design a target-based high-content screen to identify and classify compounds that exhibit differential effect on MUC16-expressing cells. We developed a coculture assay in 384-well plate containing isogenic ovarian cancer cells that are positive or negative for the MUC16 protein. High-throughput screening of our small molecule pilot library led to the identification of compounds preferentially cytotoxic to MUC16(+) or MUC16(-) cells, using a Preferential Score analysis. We compared screening results in both A2780 and SK-OV-3 ovarian cancer cells in single and coculture settings. We also identified compounds that were cytotoxic for both types of ovarian cancer cells regardless of the MUC16 status. Compounds that were preferentially targeting MUC16 cells were subsequently confirmed by caspase-induction assays. The isogenic, dual-color fluorescence strategy is an innovative approach that can effectively identify novel drug candidates, selectively targeting cancer cells that have unique molecular properties.

Indexed as

Antineoplastic AgentsCA-125 AntigenCell Line, TumorDrug Screening Assays, AntitumorFemaleFluorescenceHigh-Throughput Screening AssaysHumansMembrane ProteinsOvarian NeoplasmsAntineoplastic AgentsCA-125 AntigenMembrane ProteinsMUC16 protein, human

Identifiers

PMID21817115
PMCPMC3191303
OpenAlexW2065527903

What OpenQuestion holds

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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.