Conquering RAS - 1st Edition - ISBN: 9780128035054, 9780128035412

Conquering RAS

1st Edition

From Biology to Cancer Therapy

Authors: Asfar Azmi
eBook ISBN: 9780128035412
Hardcover ISBN: 9780128035054
Imprint: Academic Press
Published Date: 30th August 2016
Page Count: 294
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Description

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.

Key Features

  • 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

Readership

RAS researchers – basic and translational, cancer researchers, geneticists, pharmaceutical drug researchers, academic clinicians involved in RAS related trials, molecular biologists, computational biologists

Table of Contents

  • 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

Details

No. of pages:
294
Language:
English
Copyright:
© Academic Press 2017
Published:
Imprint:
Academic Press
eBook ISBN:
9780128035412
Hardcover ISBN:
9780128035054

About the Author

Asfar Azmi

Dr. Asfar S. Azmi, PhD. is an Assistant Professor in the Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan USA. He has more than a decade of research experience in the area of cancer biology and drug discovery. His translational work broadly focuses on designing, developing and testing novel small molecule drugs in a wide variety of solid tumors and hematological malignancies. His research has a special focus on oncogenic KRAS driven tumors, particularly pancreatic ductal adenocarcinoma.

Dr. Azmi utilizes cutting edge computational biology in his drug discovery work that has helped in bringing a number of agent into the clinic such as AT-101 (an advanced Bcl-2 inhibitor currently in 23 different clinical trials) and nuclear export inhibitor (Selinexor). Dr. Azmi has published over 100 peer reviewed articles and numerous editorials as well. He served as executive guest editor for 5 different thematic issues in prestigious journals such as Seminars in Cancer Biology and others. He is the editor of a book on Systems Biology in Cancer Research and Drug Discovery for Springer and another book on Molecular Diagnostics and Treatment of Pancreatic Cancer published through Elsevier Academic Press. He is the editor in Chief of Wolters Kluwer Journal Oncobiology and Targets. In summary, Dr. Azmi has proven track record of comprehensive editorial work. He brings with him vast experience necessary to undertake this important project and complete it in a timely fashion.

Affiliations and Expertise

Assistant Professor, Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA