The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory NRASQ61K melanoma. (Record no. 2702)

MARC details
000 -LEADER
fixed length control field 03135nam a22004937a 4500
008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION
fixed length control field 170505s20162016 xxu||||| |||| 00| 0 eng d
022 ## - INTERNATIONAL STANDARD SERIAL NUMBER
International Standard Serial Number 1949-2553
040 ## - CATALOGING SOURCE
Original cataloging agency Ovid MEDLINE(R)
099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC)
PMID 28157711
245 ## - TITLE STATEMENT
Title The repurposed anthelmintic mebendazole in combination with trametinib suppresses refractory NRASQ61K melanoma.
251 ## - Source
Source Oncotarget. 8(8):12576-12595, 2017 Feb 21
252 ## - Abbreviated Source
Abbreviated source Oncotarget. 8(8):12576-12595, 2017 Feb 21
253 ## - Journal Name
Journal name Oncotarget
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Year 2017
260 ## - PUBLICATION, DISTRIBUTION, ETC.
Manufacturer FY2017
266 ## - Date added to catalog
Date added to catalog 2017-05-06
520 ## - SUMMARY, ETC.
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.
546 ## - LANGUAGE NOTE
Language note English
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Antineoplastic Combined Chemotherapy Protocols/pd [Pharmacology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Cell Proliferation/de [Drug Effects]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Mebendazole/pd [Pharmacology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Melanoma/pa [Pathology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Pyridones/pd [Pharmacology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element *Pyrimidinones/pd [Pharmacology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Animals
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Antinematodal Agents/pd [Pharmacology]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Cell Line, Tumor
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element GTP Phosphohydrolases
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Humans
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Immunoblotting
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Melanoma/ge [Genetics]
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Membrane Proteins
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Mice
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Protein Array Analysis
650 ## - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element Xenograft Model Antitumor Assays
651 ## - SUBJECT ADDED ENTRY--GEOGRAPHIC NAME
Institution MedStar Franklin Square Medical Center
657 ## - INDEX TERM--FUNCTION
Medline publication type Journal Article
700 ## - ADDED ENTRY--PERSONAL NAME
Local Authors Abdussamad, Maryam
700 ## - ADDED ENTRY--PERSONAL NAME
Local Authors Zapas, John
700 ## - ADDED ENTRY--PERSONAL NAME
Local Authors Zhou, Hengbo
790 ## - Authors
All authors Abdussamad M, Atkins MB, Byers SW, Calvert V, Chen YS, Dakshanamurthy S, Fang HB, Gaur A, Petricoin EF, Rosenthal DS, Simbulan-Rosenthal CM, Zapas J, Zhou H
856 ## - ELECTRONIC LOCATION AND ACCESS
DOI <a href="https://dx.doi.org/10.18632/oncotarget.14990">https://dx.doi.org/10.18632/oncotarget.14990</a>
Public note https://dx.doi.org/10.18632/oncotarget.14990
942 ## - ADDED ENTRY ELEMENTS (KOHA)
Koha item type Journal Article
Item type description Article
Holdings
Withdrawn status Lost status Damaged status Not for loan Collection Home library Current library Date acquired Total Checkouts Full call number Barcode Date last seen Price effective from Koha item type
          MedStar Authors Catalog MedStar Authors Catalog 05/06/2017   28157711 28157711 05/06/2017 05/06/2017 Journal Article

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