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Cancer Cell. 2014 Nov 10;26(5):603-4. doi: 10.1016/j.ccell.2014.10.017. Epub 2014 Nov 10.

Combination of RAF and MEK inhibition for the treatment of BRAF-mutated melanoma: feedback is not encouraged.

Author information

1
Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: chapmanp@mskcc.org.
2
Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA.
3
Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA.

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.

PMID:
25517746
DOI:
10.1016/j.ccell.2014.10.017
[Indexed for MEDLINE]
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