Therapeutic Strategies in Cancer Biology and Pathology

Therapeutic Strategies in Cancer Biology and Pathology

1st Edition - July 26, 2013

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  • Author: Gajanan Sherbet
  • Hardcover ISBN: 9780124165700
  • eBook ISBN: 9780124165908

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Description

Currently, intensive effort is being directed toward the identification of molecular targets that can provide approaches to the development of novel therapeutic strategies in cancer management. This book focuses on metastasis-associated genes, metastasis promoter and suppressor genes, which relate specifically to behavioral alterations of cancer cells in epithelial mesenchymal transition, cancer stem cell maintenance and propagation, and to the acquisition of invasive and metastasis faculty. The function of these genes has implications for cell cycle regulation and cell proliferation and so constitute an essential element in cancer growth and dissemination. The emphasis in this book is on how appropriate these genes are as molecular targets and how practicable are the constituents of their signal transduction systems as potential candidates and how accessible they are to targeted therapy. Written in a straightforward and clear style with background information supporting the new research, this book will be useful for students and researchers in cancer therapies.

Key Features

  • Identifies molecular targets and their accessibility for therapeutic intervention
  • Provides information on biological features of tumor development and dissemination
  • Background information provided for each topic

Readership

Developmental biologists, cell biologists and cancer researchers

Table of Contents

  • Dedication

    Preface

    Abbreviations

    Introduction

    Part 1: RNA Interference in Genetic Regulation

    1. The Biogenesis and Functions of MicroRNAs

    2. Association of miRNAs with Pathogenesis

    The Genesis of DiGeorge Syndrome

    Association of the Glyoxalase Pathway with miRNA Function

    3. Are miRNAs Suitable Targets for Cancer Therapy?

    A Resumé of mTOR Signalling

    miRNAs, Cell Proliferation and Apoptosis

    miRNAs in EMT, and Cell Motility and Invasion

    miRNAs and Tumour Angiogenesis

    miRNAs, Tumour Growth, Invasion and Metastasis

    miRNAs and Chemo/Radiosensitivity of Tumours

    The Therapeutic Potential of miRNAs

    Part 2: EMT Associated Gene Targeting

    4. Hedgehog Signalling in EMT

    5. Targeted Inhibition of Hh, Wnt, TGF-β Signalling Complex

    SMO Is a GPCR Component of Hh Signalling

    Small Molecule Inhibitors of SMO

    HDAC Inhibitors Combination with Hh Inhibition

    Targeting Gli1 in Deregulated Hh Signalling

    6. Encountering Aberrant Wnt Signalling

    The Canonical and Non-canonical Wnt Routes of Signalling

    Fzd and LRP Inhibition, Dkk and SFRPs

    Fzd and DVL Interaction

    7. Therapeutic Targeting of TGF-β Signalling

    Antisense Oligonucleotide Trabedersen (AP 12009)

    Anti-TGF-β Monoclonal Antibodies

    Small Molecule Inhibitors of the TGF-β Receptor Family

    Inhibition of Type RIII Function

    8. EGFR Signalling in EMT

    E-cadherin in EGFR Signalling

    EGFR Signalling Path to EMT

    ECM and Cell Membrane Components in EGFR Signalling

    EGFR and TGF-β Signalling Pathways Interact in EMT

    Part 3: Therapeutic Deployment of Metastasis-Associated Gene Function

    9. S100A4 as a Potential Target

    The Spectrum of Biological Function of S100A4

    Influence of Wnt Signalling on S100A4 Expression

    Osteopontin an Intermediary Target of S100A4

    RAGE/NF-κB Signalling in S100A4 Function

    S100A4 Downregulates PRDM1 and VASH1 Suppressor Genes

    S100A2 Suppressor Gene and S100A4 Function

    10. MTAs in Cancer Invasion and Metastasis

    The Biology of Metastasis Promotion by MTAs

    Modulation/Inhibition of MTA Expression

    MTA Signalling Intercalates with Wnt/Notch/Hh Signalling

    Part 4: Genetic Determinants of Tumour and Metastasis Suppression

    11. Metastasis Suppressor nm23 and Manipulation of its Expression

    Manipulation of nm23 Expression as a Therapeutic Approach

    Upregulation of nm23 by Medroxyprogesterone Acetate

    Targeting S100A4 to Restore nm23 Function

    Is Tumor Suppressor p53 a Route to nm23 Manipulation?

    12. The Metastasis Suppressor KiSS-1 Gene

    The Tumor Suppressor Function of Kisseptin

    Kisseptin in Clinical Medicine

    13. KAI1 (CD82) Suppresses Metastasis, Cell Proliferation and Invasion

    Reactivation of KAI1

    14. 14-3-3 Proteins in Normal and Tumour Cell Biology

    Expression of 14-3-3σ in Tumour Progression

    How Do Other 14-3-3 Isoforms Perform in the Clinical Settting?

    14-3-3 Proteins in Regulation of Cell Proliferation

    P53 in 14-3-3 Function

    The Function of 14-3-3 via PI3K/Akt Survival Pathway

    Growth Factors and Their Receptors in 14-3-3 Function

    Regulation of Cell Cycle Checkpoints by 14-3-3 Proteins

    Do 14-3-3 Proteins Participate in DNA Repair?

    14-3-3σ and NF-κB Survival Pathway

    Does 14-3-3σ Influence Wnt Signalling?

    14-3-3 and Hh Signalling

    14-3-3 Proteins Interact with RASSF Signalling

    Do 14-3-3 Proteins Employ mTOR Signalling?

    Effects of 14-3-3 Proteins on Cell Motility and Invasion

    Therapeutic Approach with 14-3-3

    15. Suppressor Function of NDRG1

    NDRG1 Suppresses MMP Activity and Invasion

    Upregulation of NDRG1 Suppresses Cell Migration and Proliferation

    Regulation of Cell Proliferation by NDRG1 Mediated by p53

    Oestradiol and NDRG1 Expression

    Metastasis Suppression by NDRG1

    16. The ING (Inhibitor of Growth) Suppressor Gene

    17. The BRCA1 and BRCA2 Suppressor Genes

    18. BRMS1 (Breast Cancer Metastasis Suppressor 1) Gene

    19. Maspin (SerpinB5): A Postulated Tumour Suppressor

    20. EPB41L3 and CADM1 Tumour Suppressor Function

    Part 5: Signalling and Transcription Regulators as Prospective Candidates in Cancer Therapy

    Part 5. Signalling and Transcription Regulators as Prospective Candidates in Cancer Therapy

    21. Is MKK a Metastasis Suppressor?

    The MAPK Signalling Pathway

    MKK in Tumour Biology

    The Inhibitory Effects of Anthrax Lethal Toxin on MKKs

    LeTx and Cell Invasion/Motility

    LeTx Inhibits Angiogenesis

    22. RKIP Suppresses Invasion and Metastasis

    RKIP Downregulation Creates Chromosomal Instability and Abnormalities

    RKIP Inhibits Invasion and Growth of Cancer

    RKIP Downregulation is a Frequent Event in Cancer

    Pathways of RKIP Signalling

    Effects of Re-expression of RKIP on Metastatic Spread

    23. CRSP3 Metastasis Suppressor

    24. The Suppressor Function of TXNIP

    TXNIP in Cell Proliferation and Apoptosis

    TXNIP and Angiogenesis

    miRNAs in TXNIP Function

    25. The Essence of the Hippo Signalling System

    Lats (Large Tumour Suppressor) Gene Signals via Hippo

    Hippo in Cross Talk with Growth Factor Signalling

    Upstream Regulators of Hippo Are Tumour Suppressors

    RASSF Genes Are Silenced in Tumours

    RASSFs Regulate Cell Proliferation and Apoptosis

    The N-terminal RASSFs May Be Tumour Promoters

    26. HIC1 Suppressor Gene

    Silencing of HIC1 in Tumours

    A Resumé of Apoptosis Pathways

    The Alternative Reading Frame Tumour Suppressor Genes

    ARFs and Bmi-1 Function

    ARF Function and p53 Activity

    ARF Interactions with CtBP

    Do ARFs Function in Conjunction with 14-3-3σ?

    The PARP Pathway

    HIC1 is a Downstream Target of p53

    HIC1 Can Function Independently of p53

    27. The DLC Suppressor Genes

    Effects of Re-expression of DLC1

    DLC Expression in Metastatic Spread

    28. The LKB1 (STK11) Suppressor Gene

    Expression of LKB1 and Tumorigenesis

    LKB1 Suppresses Invasion and Metastasis

    Signalling Systems in Cross Talk with LKB1

    LKB1 in Cross Talk with Oestrogens and ER/HER2

    LKB1 Suppresses EMT

    LKB1 and Stem Cell Survival and Pluripotency

    LKB1, Cytoskeletal Dynamics and Cell Motility and Invasion

    Therapeutic Assessment of LKB1

    AMPK as a Therapeutic Target

    AICAR (5-aminoimidazole-4-carboxamide 1-D-ribonucleoside)

    Metformin Activates AMPK

    Does Metformin Selectively Destroy CSCs?

    Application of Metformin in Cancer Management

    29. PLCD1 Suppresses Tumorigenesis

    Loss of PLCD1 Expression in Tumours and its Biological Outcome

    30. Inhibitor of DNA Binding Proteins in Tumours

    Is ID4 a Tumour Suppressor?

    ID1, ID2 and ID3 Expression in Tumours

    IDs and Tumour Angiogenesis

    IDs in Cancer Stem Cell Propagation and Maintenance

    Do ID Proteins Activate Other Signalling Systems and Promote Cell Proliferation?

    Are IDs Suitable Therapeutic Targets?

    31. PDCD4 (Programmed Cell Death 4)

    Can PDCD4 Be Manipulated for Therapy?

    Epilogue

    References

Product details

  • No. of pages: 310
  • Language: English
  • Copyright: © Elsevier 2013
  • Published: July 26, 2013
  • Imprint: Elsevier
  • Hardcover ISBN: 9780124165700
  • eBook ISBN: 9780124165908

About the Author

Gajanan Sherbet

Dr. Gajanan V. Sherbet is Doctor of Science of London University and Fellow of the Royal College of Pathologists and the Royal Society of Chemistry. He is member of the editorial boards of many scientific and medical journals, and formerly editor of Experimental Cell Biology and Pathobiology. Dr. Sherbet’s major scientific interest is in cancer metastasis. He has focused on the role of growth factors and their signaling, and the calcium binding protein S100A4 in cell proliferation, cancer invasion and metastasis; also he is currently studying the potential of artificial neural networks for predicting breast cancer progression and prognosis. Dr. Sherbet has numerous scientific papers in international journals and has written and edited several books on cancer, such as Growth Factors and Their Receptors in Cell Differentiation, Cancer and Cancer Therapy (2011) and Therapeutic Strategies in Cancer Biology and Pathology (2013), and e-books on the role of growth factors and their receptors in cancer therapy and therapeutic strategies in cancer biology and molecular pathology.

Affiliations and Expertise

Professor, Institute for Molecular Medicine, Huntington Beach CA, USA and Professor (visiting), School of Electrical and Electronic Engineering, University of Newcastle upon Tyne, UK

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