Fig. 2

FAK-mediated signaling cascades involved in tumor progression. FAK activation is multifaceted and can be mediated by various factors, such as integrins, receptor tyrosine kinases (RTKs), mechanical stimuli, cytokines, G-protein-coupled receptors (GPCRs), and a change in intracellular pH (H+). Upon phosphorylation, FAK may induce the activation of different transduction pathways, including RAS/RAF/ERK, JNK, YAP, and PI3K/AKT/mTOR signaling. This process can lead to the regulation of relevant oncogenes, which in turn supports cancer cell survival. FAK also exerts nuclear functions, acting as a scaffold for p53 and Mdm2 while also promoting the polyubiquitination and degradation of p53. In doing so, FAK again promotes resistance to apoptosis. As shown in the diagram, the highlighted red boxes indicate targets of interest for the development of combination therapy using FAK inhibitors