Targeting FAK in human cancer: from finding to first clinical trials

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Focal Adhesion Kinase (FAK) overexpression is observed in numerous human cancers.
• FAK is implicated in key cancer processes including adhesion, motility, invasion, metastasis, survival, and angiogenesis.
• Recent research highlights FAK's role in epithelial-to-mesenchymal transition (EMT), cancer stem cells, and the tumor microenvironment.

Purpose of the Study:

• To review the multifaceted roles of FAK in cancer progression.
• To focus on novel findings regarding FAK in cancer stem cells, tumor microenvironment, EMT, invasion, and metastasis.
• To discuss emerging FAK-targeting therapeutic strategies and their challenges.

Main Methods:

• Literature review of FAK's functions and therapeutic targeting in cancer.
• Analysis of recent findings on FAK's involvement in cancer stemness, microenvironment, and metastasis.
• Evaluation of clinical trial data and translational approaches for FAK-targeted therapies.

Main Results:

• FAK exhibits both kinase-dependent and kinase-independent functions, with cytoplasmic and nuclear roles.
• Clinical trials investigating FAK inhibitors have yielded promising results, supporting its therapeutic potential.
• FAK is a critical mediator of EMT, cancer stem cell properties, and tumor microenvironment modulation.

Conclusions:

• FAK is a validated therapeutic target in oncology with significant clinical trial support.
• Targeting FAK, particularly in combination therapies, offers a promising avenue for cancer treatment.
• Future research should address challenges in FAK-targeted therapeutics and explore novel combination strategies.