Abstract
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase implicated in cancer progression, and plays a vital role in integrating environmental signals from growth factors, extracellular matrix and mechanical forces. As a scaffolding protein, FAK interacts and regulates the activity of many signaling kinases including Src, VEGFR-3, p53, PI3k and IGF-1R. In turn, FAK activity is modulated by a complex network of regulators that presents a number of therapeutic approaches to targeting FAK in cancer therapy. The ATP competitive inhibitors binds directly to FAK kinase domain to abrogate multiple downstream signaling pathways, and this class of agents lead the way in FAK inhibitor clinical development. CFAK-C4 and Y15 represents a novel class of non-ATP dependant, allosteric inhibitors that interrupt protein-protein interactions to achieve anti-cancer effects. The optimal approach to targeting FAK for cancer therapy is currently under investigation. Preliminary efficacy signals from early-phase trials suggest that FAK inhibitors may be best used in combination therapy. In addition to determining dosing schedules that is tolerable by patients, future clinical studies should include mechanistic-based pharmacodynamic studies to determine the biological active dose and explore potential predictive markers. In summary, a rich pipeline of FAK-targeting agents is entering clinical development and has the potential of improving the lives of cancer patients.
Keywords: FAK, focal adhesion kinase, drug development, cancer therapy, Anticancer, electron transfer, reactive oxygen species, oxidative stress, ArNO2 or ArNH2, physiological responsive range, exogenous AOs, chemotherapy, mutagenic effects, transformation
Anti-Cancer Agents in Medicinal Chemistry
Title: Development of Focal Adhesion Kinase Inhibitors in Cancer Therapy
Volume: 11 Issue: 7
Author(s): Wen Wee Ma
Affiliation:
Keywords: FAK, focal adhesion kinase, drug development, cancer therapy, Anticancer, electron transfer, reactive oxygen species, oxidative stress, ArNO2 or ArNH2, physiological responsive range, exogenous AOs, chemotherapy, mutagenic effects, transformation
Abstract: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase implicated in cancer progression, and plays a vital role in integrating environmental signals from growth factors, extracellular matrix and mechanical forces. As a scaffolding protein, FAK interacts and regulates the activity of many signaling kinases including Src, VEGFR-3, p53, PI3k and IGF-1R. In turn, FAK activity is modulated by a complex network of regulators that presents a number of therapeutic approaches to targeting FAK in cancer therapy. The ATP competitive inhibitors binds directly to FAK kinase domain to abrogate multiple downstream signaling pathways, and this class of agents lead the way in FAK inhibitor clinical development. CFAK-C4 and Y15 represents a novel class of non-ATP dependant, allosteric inhibitors that interrupt protein-protein interactions to achieve anti-cancer effects. The optimal approach to targeting FAK for cancer therapy is currently under investigation. Preliminary efficacy signals from early-phase trials suggest that FAK inhibitors may be best used in combination therapy. In addition to determining dosing schedules that is tolerable by patients, future clinical studies should include mechanistic-based pharmacodynamic studies to determine the biological active dose and explore potential predictive markers. In summary, a rich pipeline of FAK-targeting agents is entering clinical development and has the potential of improving the lives of cancer patients.
Export Options
About this article
Cite this article as:
Wee Ma Wen, Development of Focal Adhesion Kinase Inhibitors in Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (7) . https://dx.doi.org/10.2174/187152011796817628
DOI https://dx.doi.org/10.2174/187152011796817628 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Identification of Functional Peptides from Natural and Synthetic Products on Their Anticancer Activities by Tumor Targeting
Current Medicinal Chemistry Retraction Notice: The Benefits and Risks of Different Therapies in Preventing Postoperative Nausea and Vomiting in Patients Undergoing Thyroid Surgery
Current Drug Safety Biomarkers in the Evaluation and Management of Idiopathic Pulmonary Fibrosis
Current Topics in Medicinal Chemistry Staging of Breast Cancer with 18F-FDG PET and PET/CT
Current Medical Imaging Bridging Indigenous Knowledge and Scientific Evidence for Pharmacological Studies of <i>Phaleria macrocarpa</i>: A Systematic Review
The Natural Products Journal mTOR Inhibitors: Facing New Challenges Ahead
Current Medicinal Chemistry Synthesis and Biological Evaluation of 3-Chloro-4-(indol-3-yl)-2,5- pyrroledione Derivatives as Antitumor Agents
Letters in Drug Design & Discovery The Immune System of Cancer Patients
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cetuximab: Its Use in Combination with Radiation Therapy and Chemotherapy in the Multimodality Treatment of Head and Neck Cancer
Recent Patents on Anti-Cancer Drug Discovery An Emerging Strategy for Cancer Treatment Targeting Aberrant Glycogen Synthase Kinase 3β
Anti-Cancer Agents in Medicinal Chemistry Subject Index To Volume 7
Current Pharmaceutical Design Current and Future Challenges in Primary Sjogren’s Syndrome
Current Pharmaceutical Biotechnology Radiopharmaceuticals in Tumor Hypoxia Imaging: A Review Focused on Medicinal Chemistry Aspects
Anti-Cancer Agents in Medicinal Chemistry The Synthesis of Nano-Doxorubicin and its Anticancer Effect
Anti-Cancer Agents in Medicinal Chemistry Pathobiology and Therapeutic Implications of Tumor Acidosis
Current Medicinal Chemistry Anticancer Therapeutic Strategies Based on CDK Inhibitors
Current Pharmaceutical Design Survivin Modulators: An Updated Patent Review (2011 - 2015)
Recent Patents on Anti-Cancer Drug Discovery Is Red Meat Required for the Prevention of Iron Deficiency Among Children and Adolescents?
Current Pediatric Reviews Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients
Current Drug Safety Inhibitors of the Immunoproteasome: Current Status and Future Directions
Current Pharmaceutical Design