title: The role of the PI3K-AKT pathway in melanoma.
abstract: The PI3K (phosphatidylinositol 3-kinase)-AKT pathway is one of the most important signaling networks in cancer. There is growing evidence that activation of this pathway plays a significant role in melanoma, frequently in the setting of concurrent activation of RAS-RAF-MEK-ERK signaling. This evidence includes the identification of genetic and epigenetic events that activate this pathway in melanoma cell lines and clinical specimens. In addition, functional experiments have demonstrated important roles for the PI3K-AKT pathway in both melanoma initiation and therapeutic resistance. The availability of many inhibitors against the PI3K-AKT pathway is rapidly leading to the development of trials that will ultimately determine its clinical significance in this disease. The rational development of such therapies will be facilitated by strategies that utilize the growing understanding of the complexity of the regulation and roles of this pathway.
authors.affiliation: Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. mdavies@mdanderson.org
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases