Files and links (1)
Accepted (AM)Open Access (License Unspecified), Open
Journal article
Beneficial Effects of RAF Inhibitor in Mutant BRAF Splice Variant-Expressing Melanoma
Molecular cancer research, v 12(5), pp 795-802
01 May 2014
PMID: 24520098
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Resistance to RAF inhibitors such as vemurafenib and dabrafenib is a major clinical problem in the treatment of melanoma. Patients with mutant BRAF melanoma that progress on RAF inhibitors have limited treatment options, and drug removal from resistant tumors may elicit multiple effects. A frequent mechanism of resistance to RAF inhibitors is caused by expression of mutant BRAF splice variants. RAF inhibitor-resistant cell lines, generated in vivo, were tested as to whether or not mutant BRAF splice variants confer a fitness advantage in the presence of RAF inhibitor. Critically, cells expressing distinct mutant BRAF splice variants grow more efficiently in vitro and in vivo in the presence of the vemurafenib analog, PLX4720, compared with in the absence of inhibitor. PLX4720-treated BRAF splice variant-expressing cells exhibited levels of phospho-extracellular signal-regulated kinase (ERK) 1/2 comparable to untreated parental cells. In addition, a reduction in phospho-ERK1/2 levels following treatment with the MEK inhibitor, trametinib (GSK1120212) phenocopied the fitness benefit provided by PLX4720. These data indicate that mutant BRAF splice variant-expressing melanoma cells are benefited by defined concentrations of RAF inhibitors. (C)2014 AACR.
Metrics
Details
- Title
- Beneficial Effects of RAF Inhibitor in Mutant BRAF Splice Variant-Expressing Melanoma
- Creators
- Edward J. Hartsough - Thomas Jefferson UniversityKevin J. Basile - Thomas Jefferson UniversityAndrew E. Aplin - Thomas Jefferson University
- Publication Details
- Molecular cancer research, v 12(5), pp 795-802
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 8
- Grant note
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation R01-CA160495 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA National Cancer Center Joanna M. Nicolay Melanoma Foundation W81XWH-11-1-0385 / Department of Defense; United States Department of Defense P30CA056036 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000336483600015
- Scopus ID
- 2-s2.0-84900426582
- Other Identifier
- 991020532110504721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cell Biology
- Oncology