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Conquering RAS
From Biology to Cancer Therapy
1st Edition - August 11, 2016
Author: Asfar Azmi
Language: English
Hardback ISBN:9780128035054
9 7 8 - 0 - 1 2 - 8 0 3 5 0 5 - 4
eBook ISBN:9780128035412
9 7 8 - 0 - 1 2 - 8 0 3 5 4 1 - 2
Conquering RAS: From Biology to Cancer Therapy provides introductory knowledge on how modern RAS biology is taking shape in light of newer technological development. Each chapter i…Read more
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Conquering RAS: From Biology to Cancer Therapy provides introductory knowledge on how modern RAS biology is taking shape in light of newer technological development. Each chapter is written in a manner that emphasizes simplicity and readability for both new investigators and established researchers. While RAS biology has been intensively studied for more than three decades, we are yet to see any effective therapeutics that could interfere in the signaling cascade regulated by this master oncogene.
The book covers topics ranging from basic RAS biology, to translational biology and drug discovery applications. These topics will be appealing to basic researchers working in labs who seek deeper understanding of the modern concepts in RAS research. On the other side, the oncologist at the patient’s bedside will find the book useful as they routinely face the daunting task of treating patients that predominantly have a disease driven by oncogenic KRAS.
Brings together wide ranging topics in RAS basic and translational biology for the scientific and clinical communities
Showcases recent advancements in RAS research under one comprehensive volume
Includes video clips, color illustrations, and important website links to facilitate a clear understanding of RAS in cancer research
RAS researchers – basic and translational, cancer researchers, geneticists, pharmaceutical drug researchers, academic clinicians involved in RAS related trials, molecular biologists, computational biologists
Dedication
List of Contributors
Acknowledgments
Introduction
Section 1. RAS Cancer Biology
Chapter 1. Ras and RASSF Effector Proteins
Introduction
Ras and RASSF1
Ras and RASSF5 (NORE1)
Ras and RASSF2
Ras and RASSF3
Ras and RASSF4 (AD037)
Ras and RASSF6
Effects of RASSF Proteins on Mitogenic Ras Effectors
Therapeutic Ramifications
Conclusion
Glossary
List of Acronyms and Abbreviations
Chapter 2. Ras and the Hippo Pathway in Cancer
Introduction
The Hippo Tumor Suppressor Pathway
MST and LATS as the Central Mammalian Kinases Under the Influence of Hippo Signaling
YAP Signaling and Its Regulation by Hippo
Conclusions and Future Directions
Chapter 3. The Many Roles of Ral GTPases in Ras-Driven Cancer
Introduction
Ral Regulation
Ral Effectors
Ral in Model Systems
Ral in Tumorigenesis
Inhibition of Ral
Conclusions and Future Directions
Chapter 4. The Biology, Prognostic Relevance, and Targeted Treatment of Ras Pathway–Positive Childhood Acute Lymphoblastic Leukemia
Introduction
Childhood ALL
Ras Pathway Activation
Are Ras Pathway Mutations an Initiating or Secondary Event?
Disease Evolution
Prognostic Significance
Targeted Therapies
Conclusions
List of Acronyms and Abbreviations
Chapter 5. Oncogenic KRAS and the Inflammatory Micro-Environment in Pancreatic Cancer
Oncogenic Kras Drives Pancreatic Cancer Development
The Importance of Inflammation in PDAC Development
Inter-relation Between Oncogenic Kras and Inflammation in Pancreatic Cancer
Obesity-Related Inflammation Promotes Pancreatic Cancer Development
Potential Targets for Interventions
Conclusion
List of Acronyms and Abbreviations
Chapter 6. Activation of Ras by Post-Translational Modifications
Introduction
Ras Effectors
Post-translational Modifications of Ras
Conclusions
List of Acronyms and Abbreviations
Chapter 7. Cross Talk Between Snail and Mutant K-Ras Contributes to Pancreatic Cancer Progression
Introduction
K-ras and Pancreatic Cancer Progression
Epithelial-to-Mesenchymal Transition and Pancreatic Cancer Progression
Interplay Between K-ras and Snail in Regulating Pancreatic Fibrosis
Interplay Between K-ras and Snail in Regulating Pancreatic Inflammation
Role of K-ras and Snail in Regulating Pancreatic Cancer Stem Cells
Conclusion
Section 2. Novel Therapeutic Approaches Targeting RAS and Related Pathways
Chapter 8. Search for Inhibitors of Ras-Driven Cancers
Background
Directly Targeting Ras
Indirectly Targeting Ras
Targets and Inhibitors Identified Through Phenotypic Screening
Conclusions
List of Acronyms and Abbreviations
Chapter 9. GTP-Competitive Inhibitors of RAS Family Members
Introduction
Rationale for Targeting the RAS Active Site
A Brief History of Covalent Inhibitors
Simulations of GTP-Competitive RAS Inhibitors
An Opportunity to Covalently Target the KRAS Active Site
Limitations of SML-Class Compounds
Applicability of Cysteine Targeting of the RAS Superfamily
Conclusion
Chapter 10. Next-Generation Strategies to Target RAF
Introduction
RAF Mutations and Oncogenesis
RAF Inhibitors: Old Lessons Re-learned
Targeting RAF in RAS Mutant Tumors
Summary
Chapter 11. Targeting Metabolic Vulnerabilities in RAS-Mutant Cells
Introduction
An Introduction to Cancer Metabolism
Metabolism in RAS-Mutant Cells
Potential Therapeutic Approaches to Target Metabolism in RAS-Driven Cancer
Conclusion
Glossary
List of Acronyms and Abbreviations
Chapter 12. Blocking SIAH Proteolysis, an Important K-RAS Vulnerability, to Control and Eradicate K-RAS-Driven Metastatic Cancer
Introduction
List of Acronyms and Abbreviations
Chapter 13. Extracellular Signal-Regulated Kinase (ERK1 and ERK2) Inhibitors
Introduction
RAS Inhibitors
RAF Inhibitors
MEK Inhibitors
Direct Small Molecule Inhibitors of ERK
Conclusions and Future Directions
Chapter 14. Targeting Rho, Rac, CDC42 GTPase Effector p21 Activated Kinases in Mutant K-Ras-Driven Cancer
Introduction
Ras Superfamily
Rho Family GTPases and Cancer
Rho GTPase Effectors
P21 Activated Kinases as Effectors of GTPases
PAKs in Cancer
Group I PAKs in Cancer
Group II PAKs in Cancer
P21 Activated Kinase 4 in Pancreatic Cancer Stemness and Drug Resistance
Small Molecule Inhibitors Targeting PAKs
Allosteric PAK Modulators
Conclusions and Future Directions
List of Acronyms and Abbreviations
Index
No. of pages: 294
Language: English
Edition: 1
Published: August 11, 2016
Imprint: Academic Press
Hardback ISBN: 9780128035054
eBook ISBN: 9780128035412
AA
Asfar Azmi
Asfar Azmi, PhD, is an Assistant Professor at the Department of Oncology, Wayne State University. He has more than a decade of research experience in the area of cancer biology and drug discovery.
Dr. Azmi’s lab has made significant pre-clinical discoveries in advanced animal tumor models that helped the clinical development of new cancer drugs. Dr. Azmi has considerable experience in the area of early phase clinical research. Several agents developed by his team have gone into Phase II clinical studies. He has published more than 100 cancer research articles and has edited three additional books, among which there are the Elsevier publications Molecular Diagnostics and Treatment of Pancreatic Cancer as well as Conquering Ras. He is the recipient of numerous young investigator awards from premier scientific bodies. The National Institute of Health and pharmaceutical industry have continuously funded his lab.
Affiliations and expertise
Assistant Professor, Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA