Extracellular targeting of cell signaling in cancer strategies directed at MET and RON receptor tyrosine kinases 1st Edition by Roseann Benson, James W Janetka 1119300212 9781119300212

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ISBN-10 :  1119300212 

ISBN-13 :  9781119300212

Author:  Roseann Benson, James W Janetka 

International experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy.  With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development. A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell surface in response to extracellular ligands (growth factors.) Both kinases are oncogenes which are required by cancer cells to migrate away from the primary tumor, invade surrounding tissue and metastasize. MET and RON reside on both cancer cells and the support cells surrounding the tumor, called the microenvironment.

Extracellular targeting of cell signaling in cancer : strategies directed at MET and RON receptor tyrosine kinases 1st Table of contents:

Chapter 1: Discovery and Function of the HGF/MET and the MSP/RON Kinase Signaling Pathways in Cancer
1.1 Introduction
1.2 MET Tyrosine Kinase Receptor and its Ligand HGF: Structure
1.3 RON Tyrosine Kinase Receptor and its Ligand MSP
1.4 Targeting MSP/RON as a Therapeutic Approach in Human Cancer
1.5 Concluding Remarks
Acknowledgements
References
Chapter 2: The Role of HGF/MET and MSP/RON Signaling in Tumor Progression and Resistance to Anticancer Therapy
2.1 Introduction
2.2 HGF/MET Signaling in Cancer
2.3 MSP/RON Signaling in Cancer
2.4 Cross‐talk between MET and RON Signaling Pathways
2.5 HGF/MET and MSP/RON Signaling Elicit Resistance to Cancer Therapy
2.6 Conclusions and Perspectives
References
Chapter 3: HGF Activator (HGFA) and its Inhibitors HAI‐1 and HAI‐2: Key Players in Tissue Repair and Cancer
3.1 Introduction
3.2 Discovery of HGFA
3.3 Synthesis of HGFA Zymogen in vivo
3.4 Molecular Structure of HGFA
3.5 Substrates of HGFA in vivo
3.6 Regulation of HGFA Activity by Endogenous Inhibitors
3.7 Proposed Biological Functions of HGFA in vivo
3.8 Roles of HGFA in Cancer
3.9 Conclusions and Future Perspectives of HGFA Research in Cancer
References
Chapter 4: Physiological Functions and Role of Matriptase in Cancer
4.1 Introduction
4.2 Discovery of Matriptase
4.3 Biochemical and Functional Characteristics of Matriptase – Inhibitors, Substrates and Structure
4.4 Physiological and Pathophysiological Functions of Matriptase
4.5 Role of Matriptase in Cancer
4.6 Conclusions
References
Chapter 5: The Cell‐Surface, Transmembrane Serine Protease Hepsin: Discovery, Function and Role in Cancer
5.1 Biology of Hepsin
5.2 Hepsin in Cancer
5.3 Future Prospects
Acknowledgements
References
Chapter 6: Targeting HGF with Antibodies as an Anti‐Cancer Therapeutic Strategy
6.1 Introduction
6.2 HGF Biology
6.3 HGF in Cancer
6.4 Anti‐HGF Monoclonal Antibodies as Anti‐Cancer Therapeutic Candidates
6.5 Conclusions and Future Directions
Acknowledgements
References
Chapter 7: MET and RON Receptor Tyrosine Kinases as Therapeutic Antibody Targets for Cancer
7.1 MET as a Therapeutic Antibody Target for Cancer
7.2 Challenges in Developing MET Therapeutic Antibodies
7.3 Anti‐MET Antibody Clinical Diagnostics
7.4 Anti‐MET Antibodies in the Clinic
7.5 Additional anti‐MET Antibodies
7.6 Summary– anti‐MET Antibodies
7.7 RON as a Therapeutic Antibody Target for Cancer
7.8 Conclusions and Future Outlook
References
Chapter 8: Inhibitory Antibodies of the Proteases HGFA, Matriptase and Hepsin
8.1 Anti‐Serine Protease Antibodies for Therapeutic Applications
8.2 Antibodies can Inhibit Trypsin‐Fold Serine Proteases in Diverse Ways
8.3 Introduction to Antibodies against HGFA, Matriptase and Hepsin
8.4 Inhibitory HGFA Antibodies
8.5 Inhibitory Matriptase Antibodies
8.6 Inhibitory Hepsin Antibodies
8.7 Conclusion
References
Chapter 9: Inhibitors of the Growth‐Factor Activating Proteases Matriptase, Hepsin and HGFA: Strategies for Rational Drug Design and Optimization
9.1 Introduction
9.2 Small Molecular Weight Inhibitors of HGFA, Matriptase and Hepsin
9.3 Improving Drug‐like Properties of the Current Inhibitors: Lessons from the Oral Anti‐Coagulants
9.4 Conclusion
References
Chapter 10: Cyclic Peptide Serine Protease Inhibitors Based on the Natural Product SFTI‐1
10.1 Introduction: Naturally Occurring Polypeptide Serine Protease Inhibitors
10.2 Selective Inhibitors of Serine Proteases using the Sunflower Trypsin Inhibitor (SFTI‐1) as a Scaffold for Rational Drug Design
10.3 Normal and Pathophysiological Functions of the Human Tissue Kallikrein (KLK)‐related Serine Protease Family
10.4 Inhibitors of KLK4 Serine Protease
10.5 Potential Therapeutic Applications and Challenges
10.6 Conclusions/Future Directions
References
Chapter 11: Screening Combinatorial Peptide Libraries in Protease Inhibitor Drug Discovery
11.1 Introduction
11.2 Proteases Involved in Cancer
11.3 Identification and Optimization of Preferred Substrates
11.4 Design of Covalent Inhibitors Based on Substrates
11.5 Anticancer Drugs – How much Information do We Need?
11.6 Conclusions
Acknowledgements
References
Chapter 12: Chemical Probes Targeting Proteases for Imaging and Diagnostics in Cancer
12.1 Introduction
12.2 Chemical Probes for Proteases
12.3 Molecular Imaging of Cancer
12.4 Conclusions
Acknowledgements
References
Chapter 13: Cancer Diagnostics of Protease Activity and Metastasis
13.1 Introduction
13.2 The Proteins Identified from Patient Tumor Profiling
13.3 ELISA Assay Development
13.4 The Role of Markers for Cancer Surveillance and Tumor Monitoring (Early Detection)
13.5 Cell Signaling and the Cancer Cascade
13.6 Conclusions and Future Prospects
References
Chapter 14: Roles of Pericellular Proteases in Tumor Angiogenesis: Therapeutic Implications
14.1 Introduction
14.2 Initiation of Angiogenesis
14.3 Mechanisms of New Blood Vessel Formation
14.4 Pericellular Proteases and Angiogenesis
14.5 Novel Approaches for Targeting Tumor Angiogenesis
14.6 Summary

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