Targeting focal adhesion kinase in cancer cells and the tumor microenvironment

Academic Article

Abstract

  • Focal adhesion kinase (FAK) is an integrin-associated protein tyrosine kinase that is frequently overexpressed in advanced human cancers. Recent studies have demonstrated that aside from FAK’s catalytic activity in cancer cells, its cellular localization is also critical for regulating the transcription of chemokines that promote a favorable tumor microenvironment (TME) by suppressing destructive host immunity. In addition to the protumor roles of FAK in cancer cells, FAK activity within cells of the TME may also support tumor growth and metastasis through various mechanisms, including increased angiogenesis and vascular permeability and effects related to fibrosis in the stroma. Small molecule FAK inhibitors have demonstrated efficacy in alleviating tumor growth and metastasis, and some are currently in clinical development phases. However, several preclinical trials have shown increased benefits from dual therapies using FAK inhibitors in combination with other chemotherapies or with immune cell activators. This review will discuss the role of nuclear FAK as a driver for tumor cell survival as well as potential therapeutic strategies to target FAK in both tumors and the TME.
  • Digital Object Identifier (doi)

    Author List

  • Murphy JM; Rodriguez YAR; Jeong K; Ahn EYE; Lim STS
  • Start Page

  • 877
  • End Page

  • 886
  • Volume

  • 52
  • Issue

  • 6