[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-375857-105":59,"doc-detail-375857-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","focal-adhesion-kinase-fak-emerging-target-for-drug-resistant-malignant-tumors","Focal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors","","Malignant tumors linked to drug resistance pose major difficulties for clinicians and drug developers. Alterations in the tumor microenvironment often promote cancer cell invasion and metastasis, while rapid mutation rates and adaptive resistance mechanisms undermine long-term efficacy. This review highlights Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase, as a promising target, summarizing its structural domains and how domain-specific ligands may suppress proliferation, invasion, migration, and survival. It also addresses ongoing challenges and emerging FAK-targeting molecules.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/focal-adhesion-kinase-fak-emerging-target-for-drug-resistant-malignant-tumors/375857/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/focal-adhesion-kinase-fak-emerging-target-for-drug-resistant-malignant-tumors/375857.png","ImageObject",300,407,{"name":92,"@type":93},"Connor ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are drug-resistant malignant tumors difficult to treat?","Question",{"text":113,"@type":114},"Their high mutation rates and frequent resistance to therapy drive treatment failure. Tumor microenvironment alterations also support invasion and metastasis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What makes FAK an important target in cancer?",{"text":118,"@type":114},"FAK regulates cell adhesion, migration, proliferation, and survival. Its primary phosphorylation site (Y397) contributes to signal activation associated with tumorigenesis.",{"name":120,"@type":111,"acceptedAnswer":121},"What are the key domains of FAK and how can they be targeted?",{"text":122,"@type":114},"FAK contains an N-terminal FERM domain, a kinase domain, and a C-terminal focal adhesion targeting domain. Targeting the FERM and kinase domains with ligands can suppress cancer cell proliferation, invasion, and migration.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},375857,1790313949,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":31},687207022233,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Molecular Biology Reports (2025) 52:248  \n[https://doi.org/10.1007/s1](https://doi.org/10.1007/s1) 1033-025-10296-7  \nREVIEW  \nFocal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors  \nJaya Aakriti1 · Megh Pravin Vithalkar1 · Swastika Maity1 · Krishnaprasad Baby1 · Prabhakara R. Nagareddy2 · Yogendra Nayak1  \nReceived: 3 December 2024 / Accepted: 23 January 2025 / Published online: 20 February 2025 © The Author(s) 2025  \nAbstract  \nMalignant tumors associated with drug resistance present a significant challenge for clinicians and drug developers. Mutations and alterations within the tumor microenvironment frequently drive cancer cell invasion and metastasis. Despite identifying numerous molecular targets and lead compounds, achieving sustained efficacy remains challenging due to the rapid mutation rates and the emergence of resistance. Recently, Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase, has emerged as a promising target for inhibiting cancer progression, with several lead molecules advancing through clinical trials. FAK plays a critical role in cancer pathology by regulating cell adhesion, migration, proliferation, and survival. Its structure comprises three domains-the N-terminal FERM domain, kinase domain, and C-terminal focal adhesion targeting domain-contributing to its functional versatility. Ligands targeting the FERM and kinase domains can suppress cancer cell proliferation, invasion, and migration. The FERM domain, a member of the ezrin, radixin, and moesin family, is particularly noteworthy for its ligand-binding capabilities and potential to inhibit tumor growth. While FAKis a compelling anticancer target, challenges such as tissue-specific physiological variability and broad ligand specificity remain. This review provides a detailed analysis of FAK’s role in cancer progression and explores emerging molecules targeting FAK as potential treatments for drug-resistant malignant tumors.  \n􀀍 Yogendra Nayak[yogendra.nayak@manipal.edu](yogendra.nayak@manipal.edu)  \n1 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Madhava Nagar, Manipal576104, India  \n2 Department of Internal Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA  \nGraphical Abstract  \nKeywords Cancer · Focal adhesion kinase · FAK-structure · FAK-inhibitors · Defactinib · Clinical trials · Combination therapy  \nIntroduction  \nMalignant tumors are challenging to treat due to their high mutation rates and resistance to therapy [1] . This has led to the rise of molecular-targeted therapy, which aims to overcome resistance mechanisms. These therapies primarily focus on disrupting cancer cell signaling pathways or targeting components within the tumor microenvironment [2] . Among these, targeting signaling pathways has emerged asa prominent approach. Established drug targets include Bcl- 2, Bax, CDK, EGFR/ErbB1, ERK, FGFR, HER2/ErbB2, HGF, mTOR, MAPK, MAPK/ERK kinase, PARP, PI3K, RAF, and BRAF [3] . Similarly, drug targets within the tumor microenvironment include CTLA-4, FGFR, MHC, PD-1, PD-L1, PDGFR, TCR, and VEGFR [4] .  \nFocal Adhesion Kinase (FAK) has recently gained prominence as a crucial therapeutic target due to its potential to  \nimpede cancer progression. FAK, a 125-kDa signaling protein first identified in 1992 from chicken embryos, was initially detected using monoclonal antibodies like mAb,2a7 [5] . Known as pp125, this protein demonstrated increased phosphorylation in the presence of pp60v-src [6], and its amino acid sequence confirmed it as a cytoplasmic protein tyrosine kinase [7] .  \nThe discovery of human FAK in 1996 advanced our understanding of its roles in normal and cancer cells, including its various phosphorylation sites involved in signal transduction [8]. It was observed that FAK is critical in regulating cell adhesion, proliferation, migration, and survival [9] . Its primary ","cbCaihj6HYKHgJLE","https://ap.wps.com/l/cbCaihj6HYKHgJLE","pdf",3134783,"English","# Introduction\n## Background: drug resistance and molecular-targeted therapy\n## Focal adhesion kinase as a therapeutic target\n# Methodology\n## Database selection and search strategy\n## Criteria for inclusion and exclusion","[{\"question\":\"Why are drug-resistant malignant tumors difficult to treat?\",\"answer\":\"Their high mutation rates and frequent resistance to therapy drive treatment failure. Tumor microenvironment alterations also support invasion and metastasis.\"},{\"question\":\"What makes FAK an important target in cancer?\",\"answer\":\"FAK regulates cell adhesion, migration, proliferation, and survival. Its primary phosphorylation site (Y397) contributes to signal activation associated with tumorigenesis.\"},{\"question\":\"What are the key domains of FAK and how can they be targeted?\",\"answer\":\"FAK contains an N-terminal FERM domain, a kinase domain, and a C-terminal focal adhesion targeting domain. Targeting the FERM and kinase domains with ligands can suppress cancer cell proliferation, invasion, and migration.\"}]","Focal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors | PDF",1790216372]