Melanoma mutagenesis and aberrant cell signaling Journal Article


Authors: Bello, D. M.; Ariyan, C. E.; Carvajal, R. D.
Article Title: Melanoma mutagenesis and aberrant cell signaling
Abstract: Background: Malignant melanoma is the most fatal type of skin cancer. Traditional melanoma classification has been based on histological subtype or anatomical location. However, recent evidence suggests that melanoma comprises a group of diseases characterized by distinct molecular mutations. These mutations affect disease behavior but provide unique opportunities for targeted therapy. Methods: In this review, several signaling pathways in melanoma are described as well as how mutations of BRAF, NRAS, KIT, GNAQ, and GNA11 genes cause aberrant signaling and malignant transformation. Results: Multiple genes affecting both the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathway are mutated in melanoma. Melanomas harboring the BRAF V600E mutation have demonstrated sensitivity to both RAF and MAPK/extracellular signal regulated kinase (ERK) inhibitors in vitro and in vivo. In addition, KIT-mutant melanomas, often arising from mucosal, acral, and chronically sun-damaged skin surfaces, have shown clinical response to several inhibitors of the type III transmembrane receptor tyrosine kinase KIT. Uveal melanoma, which often harbors GNAQ or GNA11 mutations, may also be sensitive to MAPK/ERK or protein kinase C/PI3K pathway inhibition. Conclusions: Emerging knowledge of these molecular alterations has led to clinical advances in patients with melanoma. The study of known mutations and identification of new potential targets must continue in an effort to develop more effective therapies for this disease.
Journal Title: Cancer Control
Volume: 20
Issue: 4
ISSN: 1073-2748
Publisher: H. Lee Moffitt Cancer Center & Research Institute  
Date Published: 2013-10-01
Start Page: 261
End Page: 281
Language: English
PROVIDER: scopus
PUBMED: 24077403
DOI/URL:
Notes: --- - "Export Date: 1 November 2013" - "CODEN: CACOF" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Richard D Carvajal
    147 Carvajal
  2. Charlotte Eielson Ariyan
    114 Ariyan
  3. Danielle Marie Bello
    25 Bello