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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lee, Brian Y. Timpson, Paul Horvath, Lisa G. Daly, Roger J. |
| Description | Country affiliation: Australia Author Affiliation: Lee BY ( The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.); Timpson P ( The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia); Horvath LG ( The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia); Daly RJ ( St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia) |
| Abstract | Focal adhesion kinase (FAK) is a key regulator of growth factor receptor- and integrin-mediated signals, governing fundamental processes in normal and cancer cells through its kinase activity and scaffolding function. Increased FAK expression and activity occurs in primary and metastatic cancers of many tissue origins, and is often associated with poor clinical outcome, highlighting FAK as a potential determinant of tumor development and metastasis. Indeed, data from cell culture and animal models of cancer provide strong lines of evidence that FAK promotes malignancy by regulating tumorigenic and metastatic potential through highly-coordinated signaling networks that orchestrate a diverse range of cellular processes, such as cell survival, proliferation, migration, invasion, epithelial-mesenchymal transition, angiogenesis and regulation of cancer stem cell activities. Such an integral role in governing malignant characteristics indicates that FAK represents a potential target for cancer therapeutics. While pharmacologic targeting of FAK scaffold function is still at an early stage of development, a number of small molecule-based FAK tyrosine kinase inhibitors are currently undergoing pre-clinical and clinical testing. In particular, PF-00562271, VS-4718 and VS-6063 show promising clinical activities in patients with selected solid cancers. Clinical testing of rationally designed FAK-targeting agents with implementation of predictive response biomarkers, such as merlin deficiency for VS-4718 in mesothelioma, may help improve clinical outcome for cancer patients. In this article, we have reviewed the current knowledge regarding FAK signaling in human cancer, and recent developments in the generation and clinical application of FAK-targeting pharmacologic agents. |
| File Format | HTM / HTML |
| ISSN | 01637258 |
| Volume Number | 146 |
| e-ISSN | 1879016X |
| Journal | Pharmacology & Therapeutics |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2015-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Therapeutics Discipline Pharmacology Antineoplastic Agents Focal Adhesion Protein-tyrosine Kinases Neoplasms Protein Kinase Inhibitors Animals Pharmacology Therapeutic Use Cell Cycle Cell Survival Antagonists & Inhibitors Chemistry Metabolism Humans Neoplasm Metastasis Drug Therapy Neoplastic Stem Cells Journal Article Review |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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