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

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.