Combination of RAF and MEK inhibition for the treatment of BRAF-mutated melanoma: Feedback is not encouraged Journal Article

  

Authors:	Chapman, P. B.; Solit, D. B.; Rosen, N.
Article Title:	Combination of RAF and MEK inhibition for the treatment of BRAF-mutated melanoma: Feedback is not encouraged
Abstract:	In BRAF V600E melanoma patients, RAF inhibitor treatment causes a MEK-inhibitor-sensitive, RAF-inhibitor-resistant adaptive reactivation of ERK signaling. In clinical trials combining MEK and RAF inhibitors, therapeutic efficacy was modestly enhanced, suggesting the utility of inhibiting feedback-reactivated pathways. Strategies for optimally inhibiting ERK signaling should be explored. In BRAF V600E melanoma patients, RAF inhibitor treatment causes a MEK-inhibitor-sensitive, RAF-inhibitor-resistant adaptive reactivation of ERK signaling. In clinical trials combining MEK and RAF inhibitors, therapeutic efficacy was modestly enhanced, suggesting the utility of inhibiting feedback-reactivated pathways. Strategies for optimally inhibiting ERK signaling should be explored.
Keywords:	signal transduction; mitogen activated protein kinase; cancer survival; treatment response; gene mutation; raf protein; drug efficacy; monotherapy; melanoma; progression free survival; gene expression; mitogen activated protein kinase inhibitor; enzyme activation; enzyme activity; wild type; hyperkeratosis; skin carcinoma; rash; cell damage; tumor cell; retinopathy; short survey; clinical effectiveness; b raf kinase; vemurafenib; dabrafenib; trametinib; enzyme reactivation; human; skin hypertrophy
Journal Title:	Cancer Cell
Volume:	26
Issue:	5
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2014-11-10
Start Page:	603
End Page:	604
Language:	English
DOI:	10.1016/j.ccell.2014.10.017
PROVIDER:	scopus
PUBMED:	25517746
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84912065268&partnerID=40&md5=1f5770e8a96bf98b6e4fa5b1cba76efd
Notes:	Export Date: 2 January 2015 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/65894