Evidence map›Paper›PMID 28157711›Full record

ArticleOncotarget2017

The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory NRASQ61K melanoma.

Cynthia M Simbulan-Rosenthal, Sivanesan Dakshanamurthy, Anirudh Gaur, You-Shin Chen, Hong-Bin Fang, Maryam Abdussamad, Hengbo Zhou, John Zapas, Valerie Calvert, Emanuel F Petricoin and 3 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing 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

38 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
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  10. Mebendazole effectively overcomes imatinib resistance by dual-targeting BCR/ABL oncoprotein and β-tubulin in chronic myeloid leukemia cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
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  20. Double Repositioning: Veterinary Antiparasitic to Human Anticancer.International journal of molecular sciences · 2022
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Cynthia M Simbulan-RosenthalDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
Sivanesan DakshanamurthyDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
Anirudh GaurDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
You-Shin ChenDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
Hong-Bin FangDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USA.
Maryam AbdussamadMedStar Franklin Square Medical Center, Baltimore, MD, USA.
Hengbo ZhouMedStar Franklin Square Medical Center, Baltimore, MD, USA.
John ZapasMedStar Franklin Square Medical Center, Baltimore, MD, USA.
Valerie CalvertCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
Emanuel F PetricoinCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
Michael B AtkinsDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
Stephen W ByersDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
Dean S RosenthalDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.
Georgetown University Medical Center · USGeorgetown University · USMedStar Franklin Square Medical Center · USGeorge Mason University · US

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI STEPHEN W BYERS · 1990 to 2026
$71.5M
Cadherin11 in cancer & rheumatoid arthritis: Common target, common therapies? (5)R01CA170653 · NCI · GEORGETOWN UNIVERSITY · PI BYERS, STEPHEN W · 2012 to 2015
$2.4M
NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA170653
6 · The paper itself

Abstract

Structure-based drug repositioning in addition to random chemical screening is now a viable route to rapid drug development. Proteochemometric computational methods coupled with kinase assays showed that mebendazole (MBZ) binds and inhibits kinases important in cancer, especially both BRAFWT and BRAFV600E. We find that MBZ synergizes with the MEK inhibitor trametinib to inhibit growth of BRAFWT-NRASQ61K melanoma cells in culture and in xenografts, and markedly decreased MEK and ERK phosphorylation. Reverse Phase Protein Array (RPPA) and immunoblot analyses show that both trametinib and MBZ inhibit the MAPK pathway, and cluster analysis revealed a protein cluster showing strong MBZ+trametinib - inhibited phosphorylation of MEK and ERK within 10 minutes, and its direct and indirect downstream targets related to stress response and translation, including ElK1 and RSKs within 30 minutes. Downstream ERK targets for cell cycle, including cMYC, were down-regulated, consistent with S- phase suppression by MBZ+trametinib, while apoptosis markers, including cleaved caspase-3, cleaved PARP and a sub-G1 population, were all increased with time. These data suggest that MBZ, a well-tolerated off-patent approved drug, should be considered as a therapeutic option in combination with trametinib, for patients with NRASQ61mut or other non-V600E BRAF mutant melanomas.

Indexed as

AnimalsAntinematodal AgentsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCell ProliferationGTP PhosphohydrolasesHumansImmunoblottingMebendazoleMelanomaMembrane ProteinsMiceProtein Array AnalysisPyridonesPyrimidinonesXenograft Model Antitumor AssaysAntinematodal AgentsGTP PhosphohydrolasesMebendazoleMembrane ProteinsNRAS protein, humanPyridonesPyrimidinonestrametinibBRAFdrug repurposingERK pathwaymebendazolemelanoma

Identifiers

PMID28157711
PMCPMC5355037
OpenAlexW2584349229

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.