The "sWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both? Journal Article

  

Authors:	Nissan, M. H.; Solit, D. B.
Article Title:	The "sWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both?
Abstract:	Activating mutations in the BRAF gene are among the most prevalent kinase mutations in human cancer. BRAF mutations are most frequent in patients with melanoma where they occur in approximately 50% of patients with advanced disease. Remarkable clinical activity has recently been reported with highly selective RAF inhibitors in melanoma patients whose tumors harbor V600E BRAF mutations. The response rates of RAF inhibitors in patients with BRAF-mutant melanomas far exceed the activity level of any prior therapy studied in this disease. The results suggest that we have entered an era of personalized therapy for patients with metastatic melanoma in which treatment selection will be guided by BRAF mutational status. This review will discuss the strengths, weaknesses, opportunities and threats ("SWOT") of developing RAF and MEK selective inhibitors as anti-cancer therapies, recent insights into the mechanisms of intrinsic and acquired resistance to these agents, and current efforts to develop mechanism-based combination therapies. © 2011 Springer Science+Business Media, LLC.
Keywords:	signal transduction; cancer chemotherapy; protein phosphorylation; unclassified drug; gene mutation; mutation; squamous cell carcinoma; sorafenib; bevacizumab; sunitinib; drug efficacy; liver cell carcinoma; nonhuman; antineoplastic agents; capecitabine; pancreas cancer; temozolomide; cancer staging; antineoplastic agent; binding affinity; protein function; protein localization; dacarbazine; ipilimumab; melanoma; skin neoplasms; lung non small cell cancer; genetic association; gene function; enzyme inhibitor; kidney carcinoma; carcinogenesis; rash; oncogene; maculopapular rash; drug mechanism; enzyme inhibitors; colon cancer; brain metastasis; binding site; down regulation; pemetrexed; b raf kinase; raf kinases; braf; mapk; mek; eye toxicity; drug protein binding; proto-oncogene proteins b-raf; keratoacanthoma; n (2,3 dihydroxypropoxy) 3,4 difluoro 2 (2 fluoro 4 iodoanilino)benzamide; molecular pathology; 2 (2 chloro 4 iodoanilino) n cyclopropylmethoxy 3,4 difluorobenzamide; gsk 1120212; gsk 2118436; map kinase kinase kinases; retina vein occlusion; selumetinib; erk; vemurafenib; mitogen activated protein kinase kinase inhibitor; keratosis; raf kinase inhibitor; gsk2118436; plx4032; agents affecting metabolism
Journal Title:	Current Oncology Reports
Volume:	13
Issue:	6
ISSN:	1523-3790
Publisher:	Springer
Date Published:	2011-12-01
Start Page:	479
End Page:	487
Language:	English
DOI:	10.1007/s11912-011-0198-4
PROVIDER:	scopus
PUBMED:	21997758
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-81155124389&partnerID=40&md5=9ddaa9fcbd1db91e2425df375117a100
Notes:	--- - "Export Date: 9 December 2011" - "CODEN: CORUA" - "Source: Scopus"

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