Evidence map›Paper›PMID 38959709›Full record

ArticleTranslational oncology2024

Preclinical evidence for employing MEK inhibition in NRAS mutated pediatric gastroenteropancreatic neuroendocrine-like tumors.

Colin H Quinn, Andee M Beierle, Adele P Williams, Raoud Marayati, Laura V Bownes, Hooper R Market, Michael E Erwin, Jamie M Aye, Jerry E Stewart, Elizabeth Mroczek-Musulman and 2 more

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In one paragraph

Article in Translational oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

12 authors.

Colin H QuinnDivision of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL 35205, USA.
Andee M BeierleDepartment of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35222, USA.
Adele P WilliamsDivision of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL 35205, USA.
Raoud MarayatiDivision of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL 35205, USA.
Laura V BownesDivision of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL 35205, USA.
Hooper R MarketDivision of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL 35205, USA.
Michael E ErwinDivision of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL 35205, USA.
Jamie M AyeDivision of Pediatric Hematology Oncology, Department of Pediatrics, University of Alabama, Birmingham, Birmingham, AL 35233, USA.
Jerry E StewartDivision of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL 35205, USA.
Elizabeth Mroczek-MusulmanDepartment of Pathology, University of Alabama, Birmingham, Birmingham, AL 35233, USA.
Karina J YoonDepartment of Pharmacology and Toxicology, University of Alabama, Birmingham, Birmingham, AL 35233, USA.
Elizabeth A BeierleDivision of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL 35205, USA. Electronic address: elizabeth.beierle@childrensal.org.

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9M
NCI NIH HHS P30 CA013148
6 · The paper itself

Abstract

backgroundPediatric gastroenteropancreatic neuroendocrine tumors are exceedingly rare, resulting in most pediatric treatment recommendations being based on data derived from adults. Trametinib is a kinase inhibitor that targets MEK1/2 and has been employed in the treatment of cancers harboring mutations in the Ras pathway.

methodsWe utilized an established human pediatric gastroenteropancreatic neuroendocrine-like tumor patient-derived xenograft (PDX) with a known NRAS mutation to study the effects of MEK inhibition. We evaluated the effects of trametinib on proliferation, motility, and tumor growth in vivo. We created an intraperitoneal metastatic model of this PDX, characterized both the phenotype and the genotype of the metastatic PDX and again, investigated the effects of MEK inhibition.

resultsWe found target engagement with decreased ERK1/2 phosphorylation with trametinib treatment. Trametinib led to decreased in vitro cell growth and motility, and decreased tumor growth and increased animal survival in a murine flank tumor model. Finally, we demonstrated that trametinib was able to significantly decrease gastroenteropancreatic neuroendocrine intraperitoneal tumor metastasis.

conclusionsThe results of these studies support the further investigation of MEK inhibition in pediatric NRAS mutated solid tumors.

Indexed as

MEK InhibitionMetastatic diseaseNRAS mutationPatient-derived xenograftsPediatric cancerTarget therapies

Identifiers

PMID38959709
PMCPMC11269785

What Socratic holds

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Registered trials

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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 Socratic graph.