Multi-targeted molecular therapeutic approach in aggressive neuroblastoma: the effect of Focal Adhesion Kinase-Src-Paxillin system

Expert Opin Ther Targets. 2014 Dec;18(12):1395-406. doi: 10.1517/14728222.2014.952280. Epub 2014 Sep 5.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: Src; focal adhesion kinase; neuroblastoma; paxillin; small-molecule inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / metabolism
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Multiple / physiology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / physiology
  • Focal Adhesion Kinase 1 / antagonists & inhibitors*
  • Focal Adhesion Kinase 1 / metabolism
  • Humans
  • Molecular Targeted Therapy / methods*
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Paxillin / antagonists & inhibitors*
  • Paxillin / metabolism
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / metabolism

Substances

  • Antineoplastic Agents
  • PXN protein, human
  • Paxillin
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • src-Family Kinases