Journal article
In vivo MAPK reporting reveals the heterogeneity in tumoral selection of resistance to RAF inhibitors
Cancer research (Chicago, Ill.), v 73(23), pp 7101-7110
01 Dec 2013
PMID: 24121492
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Activation of the ERK1/2 mitogen-activated protein kinases (MAPKs) confers resistance to the RAF inhibitors vemurafenib and dabrafenib in mutant BRAF-driven melanomas. Methods to understand how resistance develops are important to optimize the clinical utility of RAF inhibitors in patients. Here we report the development of a novel ERK1/2 reporter system that provides a non-invasive, quantitative and temporal analysis of RAF inhibitor efficacy
in vivo
. Use of this system revealed heterogeneity in the level of ERK1/2 reactivation associated with acquired resistance to RAF inhibition. We identified several distinct novel and known molecular changes in resistant tumors emerging from treatment-naïve cell populations including BRAF V600E variants and HRAS mutation, both of which were required and sufficient for ERK1/2 reactivation and drug resistance. Our work offers an advance in understanding RAF inhibitor resistance and the heterogeneity in resistance mechanisms, which emerge from a malignant cell population.
Metrics
Details
- Title
- In vivo MAPK reporting reveals the heterogeneity in tumoral selection of resistance to RAF inhibitors
- Creators
- Kevin J. Basile - Thomas Jefferson UniversityEthan V. Abel - Thomas Jefferson UniversityNeda Dadpey - Thomas Jefferson UniversityEdward J. Hartsough - Thomas Jefferson UniversityPaolo Fortina - Thomas Jefferson UniversityAndrew E. Aplin - Thomas Jefferson University
- Publication Details
- Cancer research (Chicago, Ill.), v 73(23), pp 7101-7110
- Publisher
- American Association for Cancer Research (AACR)
- Grant note
- R01 CA125103 || CA / National Cancer Institute : NCI
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000328941200024
- Scopus ID
- 2-s2.0-84890296879
- Other Identifier
- 991020531827704721
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
- Oncology