KRAS and BRAF: Drug targets and predictive biomarkers Journal Article
| Authors: | Vakiani, E.; Solit, D. B. |
| Article Title: | KRAS and BRAF: Drug targets and predictive biomarkers |
| Abstract: | Three decades have passed since RAS was first identified as the transformative factor in the Harvey and Kirsten strains of the mouse sarcoma virus. RAS and several of its downstream effectors, including BRAF, have since been shown to be commonly mutated in broad range of human cancers and biological studies have confirmed that RAS pathway activation promotes tumour initiation, progression and metastatic spread in many contexts. With the identification of RAS mutation as a strong predictor of clinical resistance to EGFR-targeted therapies, RAS mutational testing has been incorporated into the routine clinical care of patients with colorectal and lung cancers. This article reviews the current understanding of RAS signalling as it relates to cancer biology, current efforts to develop inhibitors of RAS and its key downstream effectors and the technical challenges of RAS mutational testing in the clinical setting. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| Keywords: | unclassified drug; promoter region; missense mutation; clinical trial; review; squamous cell carcinoma; sorafenib; erlotinib; raf protein; liver cell carcinoma; drug targeting; capecitabine; temozolomide; neurotoxicity; clinical practice; colorectal cancer; unindexed drug; melanoma; controlled clinical trial; mitogen activated protein kinase kinase 1; mitogen activated protein kinase kinase 2; mitogen activated protein kinase inhibitor; lung non small cell cancer; randomized controlled trial; epidermal growth factor receptor; protein binding; gene frequency; lung cancer; cetuximab; phosphatidylinositol 3 kinase; kidney carcinoma; panitumumab; tumor suppressor gene; patient care; lung adenocarcinoma; drug mechanism; colon cancer; gefitinib; mitogen activated protein kinase 1; mitogen activated protein kinase 3; intermethod comparison; guanosine triphosphatase activating protein; drug bioavailability; cyclin dependent kinase inhibitor 2a; kras; drug half life; tumor growth; k ras protein; guanosine triphosphate; drug sensitivity; pemetrexed; protein mlh1; b raf kinase; braf; 5 (4 bromo 2 chloroanilino) 4 fluoro 1 methyl 1h benzimidazole 6 carbohydroxamic acid 2 hydroxyethyl ester; eye toxicity; mutations; keratoacanthoma; plx 4032; n (2,3 dihydroxypropoxy) 3,4 difluoro 2 (2 fluoro 4 iodoanilino)benzamide; mek inhibitors; braf inhibitors; egfr inhibitors; 2 (2 chloro 4 iodoanilino) n cyclopropylmethoxy 3,4 difluorobenzamide; gsk 1120212; gsk 2118436; protein serine threonine kinase inhibitor |
| Journal Title: | Journal of Pathology |
| Volume: | 223 |
| Issue: | 2 |
| ISSN: | 0022-3417 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2011-01-01 |
| Start Page: | 219 |
| End Page: | 229 |
| Language: | English |
| DOI: | 10.1002/path.2796 |
| PROVIDER: | scopus |
| PUBMED: | 21125676 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 4 March 2011" - "CODEN: JPTLA" - "Source: Scopus" |
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