title: Multi-targeted molecular therapeutic approach in aggressive neuroblastoma: the effect of Focal Adhesion Kinase-Src-Paxillin system.
abstract: BACKGROUND
  Nonreceptor tyrosine kinases play key roles in the integrin system. Located at the focal adhesions, they consist of large protein complexes through which the cytoskeleton connects to the extracellular matrix. The focal adhesion kinase (FAK)-Src-paxillin complex, a major mediator of the integrin pathway, contributes to cell migration and motility. Its overexpression is increased in children with advanced neuroblastoma (NB), one of the most common malignancies of childhood, with poor survival.
  
  
  METHODS
  We review the most recent data on FAK-Src-paxillin and their implications in NB, the molecular structure and the regulatory mechanisms of each molecule and their interactions and up-to-date information on their use as the newest biomarkers and their potential use as therapeutic targets in NB.
  
  
  CONCLUSIONS
  Based on the current literature, we hypothesize that combined and concurrent inhibition of the FAK-Src-Paxillin system may result in significant tumor suppression and prevention or delay of metastasis.
authors.affiliation: Drexel University College of Medicine, St. Christopher's Hospital for Children, Neonatal-Perinatal Medicine , 3601 A St., Philadelphia, PA 19134 , USA +1 215 762 7515 ; Pkratimenos@DrexelMed.edu.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kratimenos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Koutroulis
authors.forename: Dante
authors.initials: D
authors.lastname: Marconi
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Syriopoulou
authors.forename: Maria
authors.initials: M
authors.lastname: Delivoria-Papadopoulos
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D051419:Paxillin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C496061:PXN protein, human; D051419:Paxillin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases
keywords: Src; focal adhesion kinase; neuroblastoma; paxillin; small-molecule inhibitors