Beyond BRAF in melanoma Journal Article
| Authors: | Daud, A.; Bastian, B. C. |
| Article Title: | Beyond BRAF in melanoma |
| Abstract: | Recent progress in the analysis of genetic alterations in melanoma has identified recurrent mutations that result in the activation of critical signaling pathways promoting growth and survival of tumors cells. Alterations in the RAS-RAF-MAP kinase and PI3-kinase signaling pathways are commonly altered in melanoma. Mutations in BRAF, NRAS, KIT, and GNAQ occur in a mutually exclusive pattern and lead to MAP-kinase activation. Loss of PTEN function, primarily by deletion, is the most common known genetic alteration in the PI3-kinase cascade, and is commonly associated with BRAF mutations (Curtin et al., N Engl J Med 353:2135-2147, 2005; Tsao et al., Cancer Res 60:1800-1804, 2000, J Investig Dermatol 122:337-341, 2004). The growth advantage conveyed by the constitutive activation of these pathways leads to positive selection of cells that have acquired the mutations and in many instances leads to critical dependency of the cancer cells on their activation. This creates opportunities for therapeutic interventions targeted at signaling components within these pathways that are amenable for pharmacological inhibition. This concept follows the paradigm established by the landmark discovery that inhibition of the fusion kinase BCR-ABL can be used to treat chronic myelogenous leukemia (Druker et al., N Engl J Med 344:1031-037, 2001). The review will focus primarily on kinases involved in signaling that are currently being evaluated for therapeutic intervention in melanoma. © 2012 Springer-Verlag Berlin Heidelberg. |
| Keywords: | signal transduction; mitogen activated protein kinase; treatment response; gene mutation; overall survival; disease course; cancer localization; bevacizumab; erlotinib; raf protein; diarrhea; drug dose reduction; nonhuman; temozolomide; cancer staging; protein function; gene; cell survival; imatinib; unindexed drug; melanoma; drug eruption; enzyme inhibition; multiple cycle treatment; bone marrow suppression; mitogen activated protein kinase inhibitor; protein depletion; protein protein interaction; epidermal growth factor receptor; epidermal growth factor receptor 2; enzyme activation; phosphatidylinositol 3 kinase; carcinogenesis; cancer resistance; drug dose escalation; cancer genetics; cancer inhibition; cancer regression; mammalian target of rapamycin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; gefitinib; melanoma cell; ras protein; purine derivative; maximum plasma concentration; trastuzumab; drug dose increase; mammalian target of rapamycin inhibitor; protein family; epidermal growth factor receptor 3; uvea melanoma; 6 acetyl 8 cyclopentyl 5 methyl 2 [5 (1 piperazinyl) 2 pyridinylamino] 8h pyrido[2,3 d]pyrimidin 7 one; cyclin dependent kinase; everolimus; b raf kinase; g protein coupled receptor; lapatinib; braf gene; phosphatidylinositol 3 kinase inhibitor; protein defect; kit gene; nras gene; gnaq gene; fibroblast growth factor receptor; selumetinib; trametinib; g1 phase cell cycle checkpoint; pimasertib |
| Journal Title: | Current Topics in Microbiology and Immunology |
| Volume: | 355 |
| ISSN: | 0070-217X |
| Publisher: | Springer Verlag |
| Date Published: | 2012-01-01 |
| Start Page: | 99 |
| End Page: | 117 |
| Language: | English |
| DOI: | 10.1007/82_2011_163 |
| PROVIDER: | scopus |
| PUBMED: | 21826607 |
| DOI/URL: | |
| Notes: | In "Therapeutic Kinase Inhibitors" (ISBN: 978-3-642-28295-9) -- "Export Date: 1 February 2013" - "CODEN: CTMIA" - "Source: Scopus" |
