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Targeting focal adhesion kinase in cancer cells and the tumor microenvironment

James M Murphy1, Yelitza A R Rodriguez1, Kyuho Jeong1

  • 1Department of Biochemistry and Molecular Biology, University of South Alabama, College of Medicine, Mobile, AL, 36688, USA.

Experimental & Molecular Medicine
|June 10, 2020
PubMed

Insights

Focal adhesion kinase (FAK) is crucial in cancer progression and tumor microenvironment regulation. Targeting FAK, especially its nuclear role, offers promising therapeutic strategies, potentially combined with other treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Focal adhesion kinase (FAK) is a protein tyrosine kinase often overexpressed in advanced cancers.
  • FAK's role extends beyond catalytic activity to regulating chemokine transcription and tumor microenvironment (TME) modulation.
  • FAK activity in cancer cells and the TME supports tumor growth, metastasis, angiogenesis, and fibrosis.

Purpose of the Study:

  • To review the multifaceted roles of FAK in cancer.
  • To highlight the significance of FAK's cellular localization, particularly nuclear FAK, in tumor cell survival.
  • To discuss therapeutic strategies targeting FAK in both tumor cells and the TME.

Main Methods:

  • Literature review of recent studies on FAK function in cancer.
  • Analysis of FAK's role in regulating chemokine transcription and TME.
  • Evaluation of FAK inhibitors and combination therapies.

Main Results:

  • FAK overexpression is linked to advanced human cancers.
  • FAK localization influences chemokine transcription, impacting host immunity and TME.
  • FAK activity promotes angiogenesis, vascular permeability, and stromal fibrosis.
  • Small molecule FAK inhibitors show efficacy in preclinical models.
  • Combination therapies with FAK inhibitors demonstrate enhanced benefits.

Conclusions:

  • Nuclear FAK acts as a driver of tumor cell survival.
  • Targeting FAK in tumors and the TME presents a viable therapeutic avenue.
  • Combination strategies involving FAK inhibitors hold significant therapeutic potential.

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