Evidence map›Paper›PMID 38563850›Full record

ArticleJournal of neuro-oncology2024

Repurposing mebendazole against triple-negative breast cancer CNS metastasis.

Adrian J Rodrigues, Sophia B Chernikova, Yuelong Wang, Thy T H Trinh, David E Solow-Cordero, Ludmila Alexandrova, Kerriann M Casey, Elizabeth Alli, Abhishek Aggarwal, Tyler Quill and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 2 countries.

Adrian J Rodrigues *Department of Neurosurgery, Stanford School of Medicine, Stanford, CA, 94305, USA.
Sophia B Chernikova *Department of Neurosurgery, Stanford School of Medicine, Stanford, CA, 94305, USA. sophiac1@stanford.edu.
Yuelong Wang *Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
Thy T H TrinhDepartment of Neurosurgery, Stanford School of Medicine, Stanford, CA, 94305, USA.
David E Solow-CorderoHigh-Throughput Screening Knowledge Center, Sarafan ChEM-H, Stanford, CA, 94305, USA.
Ludmila AlexandrovaVincent Coates Foundation Mass Spectrometry Laboratory, Stanford University, Stanford, CA, 94305, USA.
Kerriann M CaseyDepartment of Comparative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Elizabeth AlliDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27109, USA.
Abhishek AggarwalDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Tyler QuillDepartment of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
Ashley K KoegelDepartment of Pediatric Hematology-Oncology, University of California, San Francisco, CA, 94143, USA.
Brian J FeldmanDepartment of Pediatrics, University of California, San Francisco, CA, 94143, USA.
James M FordDepartment of Medicine (Oncology), Stanford School of Medicine, Stanford, CA, 94305, USA.
Melanie Hayden-GephartDepartment of Neurosurgery, Stanford School of Medicine, Stanford, CA, 94305, USA. mghayden@stanford.edu.
Stanford Medicine · USStanford University · USUniversity of California, San Francisco · USHigh Throughput Biology (United States) · USMassachusetts General Hospital · USWake Forest University · USWest China Hospital of Sichuan University · CN

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI MICHAEL KENNEY · 2007 to 2026
$71.4M
TOOLKIT CoreU54CA261717 · NCI · STANFORD UNIVERSITY · PI Melanie Hayden Gephart · 2021 to 2026
$8.9M
Xevo TQ-XS Triple Quadrupole Mass Spectrometer SystemS10OD026962 · OD · STANFORD UNIVERSITY · PI CHIEN, ALLIS SOE-LANG · 2019 to 2019
$527k
Upgraded High-Content and High-Throughput siRNA Screening SystemS10RR026338 · NCRR · STANFORD UNIVERSITY · PI SOLOW-CORDERO, DAVID EDWARD · 2010 to 2010
$498k
NCI NIH HHS P30 CA124435NCI NIH HHS U54 CA261717NCRR NIH HHS S10 RR026338NIH HHS S10 OD026962NIH HHS S10OD026962NIH HHS U54CA261717
6 · The paper itself

Abstract

purposeTriple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD.

methodsA small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, CNS metastasis was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging and immunohistochemistry. MBZ was given orally at 50 and 100 mg/kg doses. MBZ bioavailability was assayed by mass spectrometry.

resultsBioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced leptomeningeal spread, and extended survival in brain metastasis model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model.

conclusionsWe demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC CNS metastasis. Our findings are concordant with previous efforts involving MBZ and CNS pathology and support the drug's potential utility to slow down leptomeningeal spread.

Indexed as

Cell MovementDrug RepositioningMebendazoleMice, Inbred BALB CMice, NudeTriple Negative Breast NeoplasmsAnimalsCell Line, TumorCell ProliferationCentral Nervous System NeoplasmsFemaleHumansMiceXenograft Model Antitumor AssaysMebendazoleBreast cancerDrug repurposingLeptomeningeal diseaseMebendazole

Identifiers

PMID38563850
PMCPMC11093727
OpenAlexW4393471644

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.