Search Ebook here:

Therapeutic Strategies in Cancer Biology and Pathology


Author: Gajanan Sherbet

Publisher: Elsevier

Publish Date: 31st July 2013

ISBN-13: 9780124165908

Pages: 310

Language: English



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.

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