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
-
Polo-Like Kinase 1 as a Potential Therapeutic Target for Osteosarcoma
Current Pharmaceutical Design Selective Divalent Copper Chelation for the Treatment of Diabetes Mellitus
Current Medicinal Chemistry Caveolin-1: A Promising Therapeutic Target for Diverse Diseases
Current Molecular Pharmacology Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications
Current Drug Targets Pyrrolo[2,3-d]Pyrimidines as Kinase Inhibitors
Current Medicinal Chemistry Current Molecularly Targeting Therapies in NSCLC and Melanoma
Anti-Cancer Agents in Medicinal Chemistry Role of Glioma-associated GLI1 Oncogene in Carcinogenesis and Cancertargeted Therapy
Current Cancer Drug Targets Novel Concepts in the Development of Platinum Antitumor Drugs
Current Medicinal Chemistry - Anti-Cancer Agents Platinum Compounds: A Hope for Future Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Mapping the High Throughput SEREX Technology Screening for Novel Tumor Antigens
Combinatorial Chemistry & High Throughput Screening New Advances in the Pathogenesis and Progression of Barrett’s Esophagus
Current Molecular Medicine Therapeutic Challenges in Neuroendocrine Tumors
Anti-Cancer Agents in Medicinal Chemistry Global Gastrointestinal Safety Profile of Etoricoxib and Lumiracoxib
Current Pharmaceutical Design Curcuminoid Metabolism and its Contribution to the Pharmacological Effects
Current Drug Metabolism Inhibitors of Cathepsin B
Current Medicinal Chemistry Genomic and Epigenetic Complexity of the FOXF1 Locus in 16q24.1: Implications for Development and Disease
Current Genomics Natural Products as Anti-Cancerous Therapeutic Molecules Targeted towards Topoisomerases
Current Protein & Peptide Science Helicobacter Pylori and Inflammation
Current Pharmaceutical Design TRPV1 and TRPA1 in Pulmonary Vagal Afferents and their Relations to Airway Sensitivity
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Nucleic Acids as Therapeutic Agents
Current Topics in Medicinal Chemistry