Journal
ONCOGENE
Volume 32, Issue 10, Pages 1207-1215Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.160
Keywords
acquired resistance; BRAF; ERK1/2; MEK1/2; RAS
Funding
- AstraZeneca
- Biotechnology and Biological Sciences Research Council [BBS/E/B/000C0419, BBS/E/B/000C0417, BBS/E/B/0000C199] Funding Source: researchfish
- Cancer Research UK [14867] Funding Source: researchfish
- Worldwide Cancer Research [12-1259] Funding Source: researchfish
- BBSRC [BBS/E/B/000C0417, BBS/E/B/000C0419] Funding Source: UKRI
Ask authors/readers for more resources
The ERK1/2 (extracellular signal-regulated kinase 1 and 2) pathway, comprising the protein kinases RAF (v-raf-1 murine leukemia viral oncogene homolog 1), MEK1/2 (mitogen-activated protein kinase or ERK kinase 1 and 2) and ERK1/2 is frequently de-regulated in human cancers, due to mutations in RAS or BRAF (v-raf-1 murine leukemia viral oncogene homolog B1). New, highly selective inhibitors of BRAF and MEK1/2 have shown promise in clinical trials, including in previously intractable diseases such as melanoma. However, drug-resistant tumour cells invariably emerge leading to disease progression. It is important to understand the mechanisms underlying such acquired resistance since this may lead to the development of rational strategies either to delay its onset or to overcome it once established. It also offers unique insights into the plasticity of signalling pathways, which may in turn inform our understanding of the basic biology of these pathways and lead to the validation of new drug targets. Several recent reports have identified diverse mechanisms of acquired resistance to MEK1/2 or BRAF inhibitors. In this article, we review these studies, discuss the different mechanisms, identify common themes and consider their therapeutic implications. Oncogene (2013) 32, 1207-1215; doi:10.1038/onc.2012.160; published online 7 May 2012
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available