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Therapeutic Strategies in Cancer Biology and Pathology - 1st Edition - ISBN: 9780124165700, 9780124165908

Therapeutic Strategies in Cancer Biology and Pathology

1st Edition

Author: Gajanan Sherbet
Hardcover ISBN: 9780124165700
eBook ISBN: 9780124165908
Imprint: Elsevier
Published Date: 31st July 2013
Page Count: 310
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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


Developmental biologists, cell biologists and cancer researchers

Table of Contents





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?




No. of pages:
© Elsevier 2013
31st July 2013
Hardcover ISBN:
eBook ISBN:

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


"The major motivation for this volume on cancer therapeutic strategies is to identify items of therapeutic interest in the biological functioning of high-profile metastasis suppressor and promoter genes and uncover links and nodes of their signaling pathways in order to directly or indirectly countermand the biological effects of these genes."--Reference & Research Book News, December 2013

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