Evidence map›Paper›PMID 23056589›Full record

ArticlePloS one2012

An RNA interference lethality screen of the human druggable genome to identify molecular vulnerabilities in epithelial ovarian cancer.

Geetika Sethi, Harsh B Pathak, Hong Zhang, Yan Zhou, Margret B Einarson, Vinod Vathipadiekal, Sumedha Gunewardena, Michael J Birrer, Andrew K Godwin

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. 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
2.6field-weighted citation impact, top 10% 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, 59 citations in OpenAlex.

  1. Review
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  7. Review
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  9. Frontiers in oncology · 2021
    Article
  10. Article
  11. Review
  12. Article
  13. Pleiotrophin: Activity and mechanism.Advances in clinical chemistry · 2020
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epithelial ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
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

9 authors at 5 institutions in 1 country.

Geetika SethiDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, United States of America.
Harsh B Pathak
Hong Zhang
Yan Zhou
Margret B Einarson
Vinod Vathipadiekal
Sumedha Gunewardena
Michael J Birrer
Andrew K Godwin
Fox Chase Cancer Center · USHarvard University · USThe University of Kansas Cancer Center · USDrexel University · USUniversity of Kansas Medical Center · US

Funding

Kansas BIRCWH Career Development Program Women's HealthK12HD052027 · NICHD · UNIVERSITY OF KANSAS MEDICAL CENTER · PI CARLSON, SUSAN E · 2005 to 2014
$5.0M
Exploiting Biological Networks to Improve Clinical Treatment of Ovarian CancerR01CA140323 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI GODWIN, ANDREW K. · 2010 to 2014
$2.1M
NCI NIH HHS CA140323NCI NIH HHS R01 CA140323NICHD NIH HHS K12 HD052027
6 · The paper itself

Abstract

Targeted therapies have been used to combat many tumor types; however, few have effectively improved the overall survival in women with epithelial ovarian cancer, begging for a better understanding of this deadly disease and identification of essential drivers of tumorigenesis that can be targeted effectively. Therefore, we used a loss-of-function screening approach to help identify molecular vulnerabilities that may represent key points of therapeutic intervention. We employed an unbiased high-throughput lethality screen using a 24,088 siRNA library targeting over 6,000 druggable genes and studied their effects on growth and/or survival of epithelial ovarian cancer (EOC) cell lines. The top 300 "hits" affecting the viability of A1847 cells were rescreened across additional EOC cell lines and non-tumorigenic, human immortalized ovarian epithelial cell lines. Fifty-three gene candidates were found to exhibit effects in all tumorigenic cell lines tested. Extensive validation of these hits refined the list to four high quality candidates (HSPA5, NDC80, NUF2, and PTN). Mechanistic studies show that silencing of three genes leads to increased apoptosis, while HSPA5 silencing appears to alter cell growth through G1 cell cycle arrest. Furthermore, two independent gene expression studies show that NDC80, NUF2 and PTN were significantly aberrantly overexpressed in serous adenocarcinomas. Overall, our functional genomics results integrated with the genomics data provide an important unbiased avenue towards the identification of prospective therapeutic targets for drug discovery, which is an urgent and unmet clinical need for ovarian cancer.

Indexed as

ApoptosisCarcinoma, Ovarian EpithelialCarrier ProteinsCell CycleCell Cycle ProteinsCell Line, TumorCytokinesCytoskeletal ProteinsEndoplasmic Reticulum Chaperone BiPFemaleGene Expression Regulation, NeoplasticHeat-Shock ProteinsHumansNeoplasms, Glandular and EpithelialNuclear ProteinsOvarian NeoplasmsCarrier ProteinsCell Cycle ProteinsCytokinesCytoskeletal ProteinsEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHSPA5 protein, humanNDC80 protein, humanNuclear ProteinsNUF2 protein, humanpleiotrophinRNA, Small Interfering

Identifiers

PMID23056589
PMCPMC3467214
OpenAlexW2115659801

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.