Roles and inhibitors of FAK in cancer: current advances and future directions

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that exhibits high expression in various tumors and is associated with a poor prognosis. FAK activation promotes tumor growth, invasion, metastasis, and angiogenesis via both kinase-dependent and kinase-independent pathways. Moreover, FAK is crucial for sustaining the tumor microenvironment. The inhibition of FAK impedes tumorigenesis, metastasis, and drug resistance in cancer. Therefore, developing targeted inhibitors against FAK presents a promising therapeutic strategy. To date, numerous FAK inhibitors, including IN10018, defactinib, GSK2256098, conteltinib, and APG-2449, have been developed, which have demonstrated positive anti-tumor effects in preclinical studies and are undergoing clinical trials for several types of tumors. Moreover, many novel FAK inhibitors are currently in preclinical studies to advance targeted therapy for tumors with aberrantly activated FAK. The benefits of FAK degraders, especially in terms of their scaffold function, are increasingly evident, holding promising potential for future clinical exploration and breakthroughs. This review aims to clarify FAK’s role in cancer, offering a comprehensive overview of the current status and future prospects of FAK-targeted therapy and combination approaches. The goal is to provide valuable insights for advancing anti-cancer treatment strategies.

Clinical Importance of Focal Adhesion Kinase (FAK)-Src and Paxillin Expression in Renal Cell Carcinoma

“…The FAK/Src dual kinase complex and its signalling cascade seem to play a significant role in tumorgenesis and chemotherapy resistance in many cancer types, such as head and neck, colon, breast, prostate, liver, thyroid, gliomas, pancreatic and others [16]. In several studies [16][17][18], a negative association between kinases' expression and prognosis was observed.…”

“…The FAK/Src dual kinase complex and its signalling cascade seem to play a significant role in tumorgenesis and chemotherapy resistance in many cancer types, such as head and neck, colon, breast, prostate, liver, thyroid, gliomas, pancreatic and others [16]. In several studies [16][17][18], a negative association between kinases' expression and prognosis was observed. For example, concomitant FAK, Src and paxillin tumour positivity and myelocytomatosis oncogene (MYCN) amplification had statistically significant increased mortality in children with neuroblastoma [19].…”