Abstract
Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is overexpressed and activated in many cancer types. FAK regulates diverse cellular processes, including growth factor signaling, cell cycle progression, cell survival, cell motility, angiogenesis, and the establishment of immunosuppressive tumor microenvironments through kinase-dependent and kinase-independent scaffolding functions in the cytoplasm and nucleus. Mounting evidence has indicated that targeting FAK, either alone or in combination with other agents, may represent a promising therapeutic strategy for various cancers. In this review, we summarize the mechanisms underlying FAK-mediated signaling networks during tumor development. We also summarize the recent progress of FAK-targeted small-molecule compounds for anticancer activity from preclinical and clinical evidence.
Highlights
Cancer is a leading cause of death, causing a substantial economic burden worldwide [1,2]
Focal adhesion kinase (FAK) is encoded by the protein tyrosine kinase 2 (PTK2) gene located on chromosomal region 8q24.3
FAK was initially identified as a component of the integrin-mediated signaling axis [5,6], and growing evidence indicated that FAK is involved in the regulation of diverse cellular processes, including growth factor signaling, cell cycle progression, cell survival, cell motility, angiogenesis, and the establishment of an immunosuppressive tumor microenvironment (TME) through kinase-dependent and -independent scaffolding functions in both the cytoplasm and nucleus [7,8,9,10]
Summary
Cancer is a leading cause of death, causing a substantial economic burden worldwide [1,2]. 4.1–ezrin–radixin–moesin (FERM) domain, followed by a kinase domain, and a carboxyterminal focal adhesion targeting (FAT) domain. FAK was initially identified as a component of the integrin-mediated signaling axis [5,6], and growing evidence indicated that FAK is involved in the regulation of diverse cellular processes, including growth factor signaling, cell cycle progression, cell survival, cell motility, angiogenesis, and the establishment of an immunosuppressive tumor microenvironment (TME) through kinase-dependent and -independent scaffolding functions in both the cytoplasm and nucleus [7,8,9,10]. Moesin (FERM) domain, followed by a central kinase domain and a carboxy-terminal focal adhesion targeting (FAT) domain. The PRRs provide proline-rich sequences that bind with Src homology 3 (SH3) domain-containing proteins. FAK is a promising drug target for cancer therapy, and the present study summarizes the recent progress in the development of FAK-targeted small-molecule compounds and combination therapy strategies for cancer
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