Evidence map›Paper›PMID 25596744›Full record

ArticleOncotarget2015

Group I Paks as therapeutic targets in NF2-deficient meningioma.

Hoi-Yee Chow, Biao Dong, Sergio G Duron, David A Campbell, Christy C Ong, Klaus P Hoeflich, Long-Sheng Chang, D Bradley Welling, Zeng-Jie Yang, Jonathan Chernoff

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. PAK2-driven cytoskeleton-endosome dynamics control macrophage hyperphagia and SIRPA engagement.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Genetic mutation and immune infiltration in embryonal tumor with multilayered rosettes.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024
    Article
  8. Review
  9. Article
  10. Preclinical Models of Meningioma.Advances in experimental medicine and biology · 2023
    Review
  11. Development and Utility of a PAK1-Selective Degrader.Journal of medicinal chemistry · 2022
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  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

10 authors at 4 institutions in 1 country.

Hoi-Yee ChowCancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Biao DongDepartment of Microbiology and Immunology, Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, Pennsylvania 19104, USA.
Sergio G DuronAfraxis Inc., La Jolla, California 92037, USA.
David A CampbellAfraxis Inc., La Jolla, California 92037, USA.
Christy C OngDepartment of Translational Oncology, Genentech, South San Francisco, California 94080, USA.
Klaus P HoeflichDepartment of Translational Oncology, Genentech, South San Francisco, California 94080, USA.
Long-Sheng ChangCenter for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
D Bradley WellingDepartment of Otolaryngology, The Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
Zeng-Jie YangCancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Jonathan ChernoffCancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Fox Chase Cancer Center · USAfraxis (United States) · USThe Ohio State University · USTemple University · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
The Role of p21-Activated Kinases in Malignant MesotheliomaR01CA148805 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN, TESTA, JOSEPH R. · 2011 to 2020
$4.0M
Early events of carcinoma induced by ErbB receptorsR01CA098830 · NCI · COLD SPRING HARBOR LABORATORY · PI MUTHUSWAMY, SENTHIL K · 2003 to 2013
$3.4M
NCI NIH HHS P30 CA006927NCI NIH HHS R01 CA098830NCI NIH HHS R01 CA148805
6 · The paper itself

Abstract

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas and meningiomas. Mutational inactivation of NF2 is found in 40-60% of sporadic meningiomas, but the molecular mechanisms underlying malignant changes of meningioma cells remain unclear. Because group I p21-activated kinases (Paks) bind to and are inhibited by the NF2-encoded protein Merlin, we assessed the signaling and anti-tumor effects of three group-I specific Pak inhibitors - Frax597, 716 and 1036 - in NF2-/- meningiomas in vitro and in an orthotopic mouse model. We found that these Pak inhibitors suppressed the proliferation and motility of both benign (Ben-Men1) and malignant (KT21-MG1) meningiomas cells. In addition, we found a strong reduction in phosphorylation of Mek and S6, and decreased cyclin D1 expression in both cell lines after treatment with Pak inhibitors. Using intracranial xenografts of luciferase-expressing KT21-MG1 cells, we found that treated mice showed significant tumor suppression for all three Pak inhibitors. Similar effects were observed in Ben-Men1 cells. Tumors dissected from treated animals exhibited an increase in apoptosis without notable change in proliferation. Collectively, these results suggest that Pak inhibitors might be useful agents in treating NF2-deficient meningiomas.

Indexed as

AnimalsAntineoplastic AgentsBrainCell Line, TumorCell ProliferationDoxycyclineGene Expression Regulation, NeoplasticHumansImmunoblottingMeningiomaMice, SCIDNeurofibromin 2p21-Activated KinasesPyridonesPyrimidinesReverse Transcriptase Polymerase Chain ReactionAntineoplastic AgentsDoxycyclineFRAX597Neurofibromin 2p21-Activated KinasesPAK1 protein, humanPAK2 protein, humanPAK3 protein, humanPyridonesPyrimidines

Identifiers

PMID25596744
PMCPMC4385830
OpenAlexW1557056576

What OpenQuestion holds

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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.