Targeting oncogenic BRAF in human cancer Journal Article
| Authors: | Pratilas, C. A.; Xing, F.; Solit, D. B. |
| Article Title: | Targeting oncogenic BRAF in human cancer |
| Abstract: | Mitogen Activated Protein Kinase (MAPK) pathway activation is a frequent event in human cancer and is often the result of activating mutations in the BRAF and RAS oncogenes. BRAF missense mutations, the vast majority of which are V600E, occur in approximately 8% of human tumors. These kinase domain mutations, which are non-overlapping in distribution with RAS mutations, are observed most frequently in melanoma but are also common in tumors arising in the colon, thyroid, lung, and other sites. Supporting its classification as an oncogene, V600EBRAF stimulates ERK signaling, induces proliferation, and is capable of promoting transformation. Given the frequent occurrence of BRAF mutations in human cancer and the continued requirement for BRAF activity in the tumors in which it is mutated, efforts are underway to develop targeted inhibitors of BRAF and its downstream effectors. These agents offer the possibility of greater efficacy and less toxicity than the systemic therapies currently available for tumors driven by activating mutations of MAPK pathway components. Early clinical results with the BRAF-selective inhibitors PLX4032 and GSK2118436 suggest that this strategy will prove successful in a select group of patients whose tumors are driven by oncogenic BRAF. © 2012 Springer-Verlag Berlin Heidelberg. |
| Keywords: | mitogen activated protein kinase; cancer survival; unclassified drug; somatic mutation; fatigue; squamous cell carcinoma; sorafenib; liver cell carcinoma; nonhuman; drug targeting; capecitabine; temozolomide; antineoplastic agent; mutant protein; colorectal cancer; dacarbazine; unindexed drug; melanoma; progression free survival; drug eruption; mitogen activated protein kinase kinase 1; mitogen activated protein kinase kinase 2; mitogen activated protein kinase inhibitor; protein protein interaction; lung cancer; enzyme activation; enzyme activity; kidney carcinoma; arthralgia; cancer genetics; cancer inhibition; enzyme phosphorylation; enzyme regulation; drug mechanism; malignant neoplastic disease; ras protein; feedback system; b raf kinase; phosphotransferase inhibitor; enzyme active site; n (2,3 dihydroxypropoxy) 3,4 difluoro 2 (2 fluoro 4 iodoanilino)benzamide; 2 (2 chloro 4 iodoanilino) n cyclopropylmethoxy 3,4 difluorobenzamide; chir 265; xl 281; selumetinib; vemurafenib; az 628; raf kinase inhibitor; rdea 119; dabrafenib; trametinib; pimasertib; 2 [4 (1 hydroxyimino 5 indanyl) 3 (4 pyridinyl) 1h pyrazol 1 yl]ethanol; arg 680; arq 680; arry 704; as 7030326; azd 8330; ch 126766; xl 518 |
| Journal Title: | Current Topics in Microbiology and Immunology |
| Volume: | 355 |
| ISSN: | 0070-217X |
| Publisher: | Springer Verlag |
| Date Published: | 2012-01-01 |
| Start Page: | 83 |
| End Page: | 98 |
| Language: | English |
| DOI: | 10.1007/82_2011_162 |
| PROVIDER: | scopus |
| PMCID: | PMC3508196 |
| PUBMED: | 21818706 |
| DOI/URL: | |
| Notes: | In "Therapeutic Kinase Inhibitors" (ISBN: 978-3-642-28295-9) -- "Export Date: 1 February 2013" - "CODEN: CTMIA" - "Source: Scopus" |
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