Therapeutic strategies for inhibiting oncogenic BRAF signaling Journal Article
| Authors: | Halilovic, E.; Solit, D. B. |
| Article Title: | Therapeutic strategies for inhibiting oncogenic BRAF signaling |
| Abstract: | Mitogen-activated protein kinase (MAPK) activation is a common property of human cancers and is often due to activating mutations in the BRAF and RAS genes. BRAF kinase domain mutations, the vast majority of which are V600E, occur in approximately 8% of human tumors. These mutations are non-overlapping in distribution with RAS mutations and are observed most frequently in melanoma but also in tumors arising in the colon, thyroid, lung and other sites. V600E BRAF mutation stimulates extracellular signal-regulated kinase (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 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 therapeutic efficacy than the currently available systemic therapies for tumors driven by activating mutations in the MAPK pathway. © 2008 Elsevier Ltd. All rights reserved. |
| Keywords: | signal transduction; mitogen activated protein kinase; unclassified drug; gene mutation; mutation; clinical trial; review; sorafenib; drug efficacy; liver cell carcinoma; nonhuman; unspecified side effect; antineoplastic agents; drug approval; antineoplastic agent; protein function; neoplasms; animals; melanoma; enzyme inhibition; mitogen activated protein kinase inhibitor; protein kinase inhibitor; lung non small cell cancer; antineoplastic activity; tumor xenograft; kidney carcinoma; oncogene; colon cancer; heat shock protein 90 inhibitor; tanespimycin; malignant neoplastic disease; inhibition kinetics; ras protein; drug bioavailability; ic 50; malignant transformation; b raf kinase; raf kinases; 5 (4 bromo 2 chloroanilino) 4 fluoro 1 methyl 1h benzimidazole 6 carbohydroxamic acid 2 hydroxyethyl ester; proto-oncogene proteins b-raf; mutant; plx 4032; n (2,3 dihydroxypropoxy) 3,4 difluoro 2 (2 fluoro 4 iodoanilino)benzamide; tanespimycin hydroquinone; nvp auy 922; 2 (2 chloro 4 iodoanilino) n cyclopropylmethoxy 3,4 difluorobenzamide; snx 5422; map kinase kinase kinases; plx 4720; xl 281; cnf 2024; raf 265; az 628; bbii 021; cnf bbii 021; raf kinase inhibitor; rdea 119; rdea 436; sb 590885 |
| Journal Title: | Current Opinion in Pharmacology |
| Volume: | 8 |
| Issue: | 4 |
| ISSN: | 1471-4892 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2008-08-01 |
| Start Page: | 419 |
| End Page: | 426 |
| Language: | English |
| DOI: | 10.1016/j.coph.2008.06.014 |
| PUBMED: | 18644254 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 27" - "Export Date: 17 November 2011" - "CODEN: COPUB" - "Source: Scopus" |
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