Evidence map›Paper›PMID 26109099›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015

Mevalonate Pathway Antagonist Suppresses Formation of Serous Tubal Intraepithelial Carcinoma and Ovarian Carcinoma in Mouse Models.

Yusuke Kobayashi, Hiroyasu Kashima, Ren-Chin Wu, Jin-Gyoung Jung, Jen-Chun Kuan, Jinghua Gu, Jianhua Xuan, Lori Sokoll, Kala Visvanathan, Ie-Ming Shih and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 4 pooled it
1.9field-weighted citation impact, top 16% 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

42 citing papers in PubMed, 4 syntheses or guidelines pooled it, 61 citations in OpenAlex.

  1. Pooled it
  2. Statins as Repurposed Drugs in Gynecological Cancer: A Review.International journal of molecular sciences · 2022
    Pooled it
  3. Pooled it
  4. Pooled it
  5. The emerging role of cholesterol metabolism in gynecologic cancer development and therapy.Apoptosis : an international journal on programmed cell death · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
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  15. Drug repurposing-an emerging strategy in cancer therapeutics.Naunyn-Schmiedeberg's archives of pharmacology · 2022
    Review
  16. Article
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  18. Review
  19. Statins: a repurposed drug to fight cancer.Journal of experimental & clinical cancer research : CR · 2021
    Review
  20. 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

11 authors at 2 institutions in 3 countries.

Yusuke KobayashiDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
Hiroyasu KashimaDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Ren-Chin WuDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Jin-Gyoung JungDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Jen-Chun KuanDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Jinghua GuDepartment of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
Jianhua XuanDepartment of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia.
Lori SokollDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Kala VisvanathanThe Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Ie-Ming ShihDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Department of Gynecology/Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Tian-Li WangDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Department of Gynecology/Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland. tlw@jhmi.edu.
Johns Hopkins University · USVirginia Tech · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Characterizing Notch3 Signaling in Ovarian CancerR01CA148826 · NCI · JOHNS HOPKINS UNIVERSITY · PI WANG, TIAN-LI · 2011 to 2015
$1.7M
TARGETING SPLEEN TYROSINE KINASE IN CHEMORESISTANT OVARIAN CARCINOMAR21CA187512 · NCI · JOHNS HOPKINS UNIVERSITY · PI WANG, TIAN-LI · 2014 to 2015
$388k
Tumor Suppressor Role of ARID1AR21CA165807 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHIH, IE-MING · 2012 to 2013
$375k
NCI NIH HHS CA148826NCI NIH HHS CA165807NCI NIH HHS CA187512NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA148826NCI NIH HHS R21 CA165807NCI NIH HHS R21 CA187512
6 · The paper itself

Abstract

purposeStatins are among the most frequently prescribed drugs because of their efficacy and low toxicity in treating hypercholesterolemia. Recently, statins have been reported to inhibit the proliferative activity of cancer cells, especially those with TP53 mutations. Because TP53 mutations occur in almost all ovarian high-grade serous carcinoma (HGSC), we determined whether statins suppressed tumor growth in animal models of ovarian cancer. EXPERIMENTAL

designTwo ovarian cancer mouse models were used. The first one was a genetically engineered model, mogp-TAg, in which the promoter of oviduct glycoprotein-1 was used to drive the expression of SV40 T-antigen in gynecologic tissues. These mice spontaneously developed serous tubal intraepithelial carcinomas (STICs), which are known as ovarian cancer precursor lesions. The second model was a xenograft tumor model in which human ovarian cancer cells were inoculated into immunocompromised mice. Mice in both models were treated with lovastatin, and effects on tumor growth were monitored. The molecular mechanisms underlying the antitumor effects of lovastatin were also investigated.

resultsLovastatin significantly reduced the development of STICs in mogp-TAg mice and inhibited ovarian tumor growth in the mouse xenograft model. Knockdown of prenylation enzymes in the mevalonate pathway recapitulated the lovastatin-induced antiproliferative phenotype. Transcriptome analysis indicated that lovastatin affected the expression of genes associated with DNA replication, Rho/PLC signaling, glycolysis, and cholesterol biosynthesis pathways, suggesting that statins have pleiotropic effects on tumor cells.

conclusionsThe above results suggest that repurposing statin drugs for ovarian cancer may provide a promising strategy to prevent and manage this devastating disease.

Indexed as

AnimalsAntineoplastic AgentsCarcinoma in SituCell Line, TumorCell ProliferationDisease Models, AnimalDNA ReplicationFemaleHumansLovastatinMevalonic AcidMiceOvarian NeoplasmsSignal TransductionTumor Suppressor Protein p53Antineoplastic AgentsLovastatinMevalonic AcidTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID26109099
PMCPMC4609247
OpenAlexW1895039234

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.