title: Clinical importance and potential use of small molecule inhibitors of focal adhesion kinase.
abstract: Since its first description Focal Adhesion Kinase (FAK), a cytoplasmatic tyrosine kinase, has been implicated in the formation and progression of solid and liquid malignant tumors. Therefore orally available selective small molecule inhibitors of FAK have been developed, three of them (PF-562-271, PF-04554878 and GSK2256098) are already in clinical testing. This review discusses the recent data obtained from these Phase 1 trials. We also discuss available data on the mechanisms of action of these inhibitors in carcinogenesis and demonstrate that FAK plays an important role in neoangiogenesis which is a crucial step in cancer growth.
authors.affiliation: University Medical Center Hamburg - Eppendorf, Hubertus Wald University Cancer Center Hamburg, Department of Oncology/Hematology with Sections BMT and Pneumology, Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schultze
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
mesh_terms: D000631:Aminopyridines / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D051418:Focal Adhesion Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; C000600809:GSK2256098; D006877:Hydroxamic Acids; D007211:Indoles; C527797:N-methyl-N-(3-((2-(2-oxo-2,3-dihydro-1H-indol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino)-methyl)-pyridin-2-yl)-methanesulfonamide; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases