Molecular Diagnostics and Treatment of Pancreatic Cancer

Molecular Diagnostics and Treatment of Pancreatic Cancer

Systems and Network Biology Approaches

1st Edition - April 14, 2014

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  • Author: Asfar Azmi
  • Hardcover ISBN: 9780124081031
  • eBook ISBN: 9780124079465

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Molecular Diagnostics and Treatment of Pancreatic Cancer describes the different emerging applications of systems biology and how it is shaping modern pancreatic cancer research. This book begins by introducing the current state of the art knowledge, trends in diagnostics, progress in disease model systems as well as new treatment and palliative care strategies in pancreatic cancer. Specific sections are dedicated to enlighten the readers to newer discoveries that have emerged from gene expression profiling, proteomics, metabolomics and systems level analyses of pancreatic cancer datasets. First of a kind and novel network strategies to understand oncogenic Kras signaling in pancreatic tumors are presented. The attempts to computationally model and prioritize microRNAs that cause pancreatic cancer resistance are also highlighted. Addressing this important area, Molecular Diagnostics and Treatment of Pancreatic Cancer provides insights into important network evaluation methodologies related to pancreatic cancer related microRNAs targetome. There are dedicated chapters on critical aspects of the evolving yet controversial field of pancreatic cancer stems cells. The work concludes by discussing the applications of network sciences in pancreatic cancer drug discovery and clinical trial design.

Key Features

  • Encompasses discussion of innovative tools including expression signatures in cell lines, 3D models, animal xenograft models, primary models and patient derived samples, aiding subversion of traditional biology paradigms, and enhancing comprehension across conventional length and temporal scales
  • Coverage includes novel applications in targeted drugs, polypharmacology, network pharmacology and other related drug development arenas – helping researchers in pancreatic cancer drug discovery
  • Summarizes many relevant computational and clinical references from fast-evolving literature
  • Comprehensive glossary helps newer readers understand technical terms and specialized nomenclature


Basic pancreatic cancer researchers, bioinformaticians, and clinicians

Table of Contents

    • Dedication
    • Preface
    • Acknowledgments
    • Section I. Current Trends and Advances in Pancreatic Cancer
      • Chapter 1. Epidemiology, Treatment, and Outcome of Pancreatic Cancer
        • Introduction
        • Epidemiology and Etiology of Pancreatic Cancer
        • Types of Pancreatic Cancer
        • Clinical Presentation of Pancreatic Cancer
        • Diagnosis of Pancreatic Cancer
        • Treatment of Pancreatic Cancer
        • Potentially Curative Surgical Treatment
        • Adjuvant and Neoadjuvant Treatment
        • Prognosis of Pancreatic Cancer
        • Outlook
      • Chapter 2. Advances in Primary Cell Culture of Pancreatic Cancer
        • Introduction
        • Cell Culture of PDAC
        • Isolation and Establishment Procedure
        • Characterization of Cell Cultures
        • Morphology
        • Genotyping
        • Phenotyping
        • Second Level of Biological Models
        • Three-Dimensional Cell Cultures
        • In Vivo Models
        • Applications
        • Conclusion
      • Chapter 3. Multimodal Therapies for Pancreatic Cancer
        • Introduction
        • Conclusion
      • Chapter 4. The Role of Notch Signaling Pathway in the Progression of Pancreatic Cancer
        • Introduction
        • Notch Signaling Pathway
        • The Role of Notch in PC
        • Notch Inhibition is a Novel Strategy for PC Treatment
        • Understanding Notch Signaling through Systems Biology
        • Conclusion
    • Section II. Gene Expression Profiling and Bioinformatics Analysis in Pancreatic Cancer
      • Chapter 5. Bioinformatics Analysis of Pancreas Cancer Genome in High-Throughput Genomic Technologies
        • Introduction
        • Heterogeneity and Quality of Samples for High-Throughput Genomic Technologies
        • Microarrays
        • Next-Generation Sequencing
        • Databases and Resources
        • Conclusion and Future Perspectives
      • Chapter 6. Statistical Analysis of High-Dimensional Data for Pancreatic Cancer
        • Introduction
        • LASSO Penalized Cox Regression
        • Doubly Regularized Cox Regression
        • Pancreatic Cancer Survival Analysis
      • Chapter 7. Gene Expression Profiling in Pancreatic Cancer
        • Introduction
        • Summary
      • Chapter 8. Genetic Susceptibility and Risk of Pancreatic Cancer
        • Introduction
        • Familial Risk of Pancreatic Cancer
        • Rare, High-Risk Pancreatic Cancer Susceptibility Genes and Multicancer Syndromes
        • Common, Low-Risk Pancreatic Cancer Susceptibility Loci
        • Common Pancreatic Cancer Risk Loci in Non-European Populations
        • Pathway Analyses of Pancreatic Cancer GWAS Data Sets
        • Future GWAS and Gene Mapping Approaches
        • Websites
    • Section III. Pancreatic Cancer Proteomics
      • Chapter 9. Proteomics in Pancreatic Cancer Translational Research
        • Introduction
        • Overview of Proteomics Technologies
        • Proteomics Study of Pancreatic Tissue
        • Blood Biomarker Discovery
        • Analysis of Pancreatic Juice and Cyst Fluid
        • Functional and Hypothesis-Driven Proteomic Studies
        • Post-translational Modifications
        • Summary
      • Chapter 10. Proteomic Differences and Linkages between Chemoresistance and Metastasis of Pancreatic Cancer Using Knowledge-Based Pathway Analysis
        • Introduction
        • Proteomic Analysis at Subcellular Level
        • Protein Identification and Data Compiling
        • Comparative Analysis of Differentially Expressed Proteins
        • Biological Network Analysis
        • Canonical Pathway Analysis Using MetaCore™
        • Vimentin Expression and Chemoresistance
        • Conclusion
      • Chapter 11. RNAi Validation of Pancreatic Cancer Antigens Identified by Cell Surface Proteomics
        • Introduction
        • Summary
    • Section IV. Systems and Network Understanding of Pancreatic Cancer Signaling
      • Chapter 12. The Significance of the Feedback Loops between Kras and Ink4a in Pancreatic Cancer
        • Introduction
        • Threshold of Kras Activation
        • Kras Effector Pathways in PDAC Development
        • Negative versus Positive Feedback Loops between Kras and Ink4a
        • Ink4a against microRNAs in the Control of Kras
        • Concluding Remarks
      • Chapter 13. Systems Biology of Pancreatic Cancer Stem Cells
        • Introduction
        • The Complexity of Pancreatic Cancer
        • Why Systems Biology is Needed for PC
        • PC Therapy Resistance and the Role of Cancer Stem Cells
        • Isolation and Biological Characterization of PC CSCs
        • Systems and Pathway Analysis of CSCs
        • Systems Analysis of PC CSC microRNA Network
        • Summary and Future Directions
      • Chapter 14. Characterizing the Metabolomic Effects of Pancreatic Cancer
        • Introduction
        • Conclusion
      • Chapter 15. Prioritizing Diagnostic, Prognostic, and Therapeutic MicroRNAs in Pancreatic Cancer: Systems and Network Biology Approaches
        • An Introduction and Brief Overview of MicroRNAs
        • MicroRNAs and Disease Priming and Progression
        • Diagnostic, Prognostic, and Therapeutic Value of miRNAs in Pancreatic Cancer
        • Prioritizing miRNAs from Pancreatic Biospecimens Using Pathway Tools
        • Clinical Targeting of miRNAs
        • Implications—New Hope or Wild-Goose Chase?
        • Conclusion
    • Section V. Systems Approaches to Pancreatic Cancer Therapeutics
      • Chapter 16. Integration of Protein Network Activation Mapping Technology for Personalized Therapy: Implications for Pancreatic Cancer
        • Introduction
        • Defective Protein Signaling Networks Underpin Tumorigenesis
        • Reverse Phase Protein Microarrays as a Tool for Personalized Cancer Therapy
        • Pre-analytical Factors Influence Phosphoprotein Pathway Activation Mapping
        • Case Studies in Pathway Activation Mapping of Human Cancer
        • Generation of a Cellular Circuit Diagram for Patient Management: A Summary
      • Chapter 17. Computational and Biological Evaluation of Radioiodinated Quinazolinone Prodrug for Targeting Pancreatic Cancer
        • Introduction to EMCIT Concept
        • Computational Evaluation
        • Sequence Alignment of Extracellular Sulfatase
        • Biological Evaluation
        • Discussion
        • Conclusions
      • Chapter 18. Systems and Network Pharmacology Strategies for Pancreatic Ductal Adenocarcinoma Therapy: A Resource Review
        • Introduction
        • Need for Revisiting the Progression Model of PDAC: Departure from Genes to Network
        • Defining Biological Networks
        • Network Pharmacology to Unwind PDAC microRNA Complexity
        • Network Pharmacology in Drug Repositioning for PDAC
        • Networks in Polypharmacology Strategies against PDAC
        • Conclusions and Future Perspectives
    • Index

Product details

  • No. of pages: 458
  • Language: English
  • Copyright: © Academic Press 2014
  • Published: April 14, 2014
  • Imprint: Academic Press
  • Hardcover ISBN: 9780124081031
  • eBook ISBN: 9780124079465

About the Author

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

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