Chemistry and Pharmacology of Anticancer Drugs  book cover
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2nd Edition

Chemistry and Pharmacology of Anticancer Drugs




  • Available for pre-order. Item will ship after March 18, 2021
ISBN 9781439853269
March 18, 2021 Forthcoming by CRC Press
584 Pages 539 B/W Illustrations

 
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Book Description

While drug therapies developed in the last 80 years have markedly improved treatment outcomes and the management of some types of cancers, the lack of effectiveness and side-effects associated with the most common treatment types remain unacceptable.  However, recent technological advances are leading to improved therapies based on targeting distinct biological pathways in cancer cells. Chemistry and Pharmacology of Anticancer Drugs is a comprehensive survey of all families of anticancer agents and therapeutic approaches currently in use or in advanced stages of clinical trials, including biological-based therapies.

The book is unique in providing molecular structures for all anticancer agents, discussing them in terms of history of development, chemistry, mechanism of action, structure-function relationships and pharmacology. It also provides relevant information on side effects, dosing, and formulation. The authors, renowned scientists in cancer research and drug discovery, also provide up-to-date information on the drug discovery process, including discussions of new research tools, tumour-targeting strategies, and fundamental concepts in the relatively new areas of precision medicine and chemoprevention.

Chemistry and Pharmacology of Anticancer Drugs is an indispensable resource for cancer researchers, medicinal chemists and other biomedical scientists involved in the development of new anticancer therapies. Its breadth of coverage, clear explanations and illustrations also make it suitable for undergraduate and postgraduate courses in medicine, pharmacy, nursing, dentistry, nutrition, the biomedical sciences and related disciplines.

Key Features:

  • Summarizes the fundamental causes of cancer, modes of treatment, and strategies for cancer drug discovery
  • Brings together a broad spectrum of information relating to the chemistry and pharmacology of all families of anticancer agents and therapies
  • Includes up-to-date information on cutting-edge aspects of cancer treatments such as biomarkers, pharmacogenetics and pharmacogenomics
  • Features new chapters on the Evolution of Anticancer Therapies, Antibody-Based Therapies and Cancer Chemoprevention

Web-Site Support:

It is recognized that the field of drug discovery in the oncology is very fast moving, and so the Second Edition of this book will have a Companion Website offering regular updates to the twelve chapters useful for both students and instructors. These updates will include new developments such as the results of pivotal clinical trials and new drug approvals. Another section will provide references to publications for key studies in the oncology area as soon as they are published, and another section will contain a list of key oncology-related websites including those that contain videos relating to cancer agents and their mechanisms of action. For instructors, PowerPoint files containing slides of all the figures and tables for each chapter will be provided for teaching purposes. For students, there are plans to provide quizzes to assist with their learning of the different drug families and types of therapies.

Table of Contents

1. Introduction to Cancer. 1.1. Incidence and Mortality. 1.2. Terminology. 1.3. Metastases. 1.4 Diagnosis and Screening. 1.5. Tumorigenesis: The Formation of Cancer Cells. 1.6. The Causes of Cancer. 1.7. Treatments. 1.8. Accessibility of Therapeutic Agents to Tumour Cells. 1.9. Limiting the Toxicity of Chemotherapeutic Agents. 1.10. Overview of Mechanisms of Action of Chemotherapeutic Agents. 1.11. Drug Resistance. 1.12. Combination Chemotherapy. 1.13. Use of Adjuvants. 1.14. Cost of Cancer Care. 1.15. Conclusions. 2. The Evolution of Anticancer Therapies. 2.1. Introduction. 2.2 The Discovery of New Anticancer Agents. 2.3. Research Tools and Methodologies for Drug Discovery. 2.4. Funding the Discovery of New Anticancer Agents. 2.5. Conclusions and the future of Drug Discovery. 3. Antimetabolites. 3.1. Introduction. 3.2. Dihydrofolate reductase (DHFR) Inhibitors. 3.3. Thymidylate synthase Inhibitors. 3.4. Purine antimetabolites. 3.5. Pyrimidine antimetabolites. 3.6. Adenosine deaminase Inhibitors. 3.7. Ribonucleotide reductase Inhibitors. 3.8. Conclusions. 4. Anti-tubulin Agents. 4.1. Introduction. 4.2. Vinca alkaloids. 4.3. Halichondrin b analogues. 4.4. The taxanes. 4.5. The epothilones. 4.6. New Approaches to Targeting Microtubule-related Mechanisms. 4.7. Conclusions. 5. Nucleic Acids as Therapeutic Targets and Agents. 5.1. Introduction. 5.2. Alkylating Agents. 5.3. Cross-linking Agents. 5.4. Intercalating Agents. 5.5. Topoisomerase Inhibitors. 5.6. DNA-cleaving Agents. 5.7. Nucleic Acid Targeting. 5.8. DNA Repair Inhibitors. 5.9. Epigenetic-based Therapies. 5.10. Radio- and Chemo-sensitizing and Protecting Agents. 5.11. Gene Therapy. 5.12. Conclusions. 6. Small-Molecule Targeted Therapies. 6.1 Introduction. 6.2. Protein Kinase Inhibitors.  6.3. Hedgehog Pathway Inhibitors. 6.4. Cell Cycle (CDK) Inhibitors. 6.5. Proteasome Inhibitors. 6.6 Phosphatidylinositol 3-Kinase (PI3K/AKT/mTOR) Pathway Inhibitors. 6.7 Apoptosis Inhibitors6.8. HDM2-p53 Interaction Inhibitors. 6.9. Retinoids. 6.10. Antimetastatic Agents. 6.11. Heat Shock Protein (HSP) Inhibitors. 6.12. Conclusions. 7. Antibody-based Therapies. 7.1 Introduction. 7.2 Antibodies as Single Agents (Naked Mabs). 7.3. Antibody Conjugates ("Immunoconjugates"). 7.4. Bi-specific Antibodies. 7.5. Conclusion. 8. Endocrine Therapies. 8.1 Introduction. 8.2. Breast Cancer. 8.3. Prostate Cancer. 8.4. Neuroendocrine Tumours (NETS). 8.5. Sex Hormones. 8.6. Mitotane (Lysodren®). 8.7. Sulfatase Inhibitors. 8.8 Conclusions. 9. Immunomodulatory Therapies. 9.1. Introduction. 9.2 Cytokines. 9.3. Vaccines. 9.4. Adoptive Cell-based Therapies. 9.5 Small-molecule Immunomodulatory Agents. 9.6 Conclusions. 10. Alternative Tumour Targeting Strategies.  10.1. Introduction. 10.2. Vascular-targeting Strategies. 10.3. Hypoxia-based Approaches. 10.4. Enzyme-based Approaches. 10.5. Nanoparticles and Conjugate Technologies. 10.6. Photoactivated Therapies. 10.7. Ultrasound Ablation Approaches. 10.8. Electromagnetic Approaches. 10.9. Radioactive Nanoparticles. 10.10. Intracranial Delivery. 10.11. Boron Neutron Capture Therapy (BNCT). 10.12. Conclusions. 11. The Precision Medicine Approach in Oncology. 11.1. Introduction and Background. 11.2. Uses of Genomic Information. 11.3. Genetic Variability and SNPS. 11.4. Components of the Precision Medicine Approach. 11.5. Technologies in Personalised Medicine. 11.6. Applications of Precision Medicine in Oncology. 11.7. Conclusions and the Future of Precision Medicine in Oncology. 12. Chemopreventive Agents. 12.1. Introduction. 12.2. Potential Mechanisms of Chemoprevention. 12.3. Challenges Associated with the Evaluation of Chemopreventive Agents. 12.4. Naturally Occurring Chemopreventive Agents. 12.5. Synthetic Chemopreventive Agents. 12.6. Conclusions.

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Author(s)

Biography

David Thurston is Emeritus Professor of Drug Discovery in the Institute of Pharmaceutical Science (IPS) at King’s College London. He has a first degree in pharmacy, an MSc in Precision Medicine and a PhD in synthetic medicinal chemistry, and has worked at two schools of pharmacy in the USA (University of Texas at Austin and Kentucky Colleges of Pharmacy) and four in the UK (the Portsmouth, Nottingham, London University and King’s College School of Pharmacy). David’s academic research team discovered the first C8-linked sequence-selective DNA-interactive PBD dimer, analogues of which are now used as the payload component for Antibody-Drug Conjugates (ADCs) in development by a number of companies world-wide as cancer therapies (e.g., Loncastuximab teserine). David has co-founded a number of oncology biotech companies including Spirogen Ltd in 2000 (which commercialized the PBD dimers, and was acquired by AstraZeneca/Medimmune in 2013), and Femtogenix Ltd in 2015 (which works on next-generation sequence-selective DNA-interactive ADC payloads, and for which he still acts as CSO).

During his academic career, David has supervised numerous PhD students and postdoctoral research fellows, and has been the PI of several major Program Grants from funders including Cancer Research UK. He has many publications in medicinal chemistry/chemistry journals and books, and is currently Editor-in-Chief of the Drug Discovery book series of the Royal Society of Chemistry.

Ilona Pysz has a first degree in Forensic Science, an MSc in Cancer Pharmacology and a PhD in Pharmaceutical Science in which she produced a number of novel Antibody-Drug Conjugates (ADCs), and developed a hydrophobicity assay which allows the physico-chemical properties of ADC payloads to be evaluated and compared. She has previously worked within the Bioanalysis and Safety Assessment (Toxicology) departments at Covance Inc (where she was responsible for overall pre-clinical study coordination of both in-house and external research projects), the drug discovery department at Femtogenix Ltd (where she worked on the development of novel ADC conjugation strategies and managed ADC development projects), and is now in a clinical research position at Medpace, Inc. Ilona has published widely in the cancer drug discovery area, has given presentations at international conferences, and is a multiple author in the Royal Society of Chemistry Drug Discovery book "Cytotoxic Payloads for Antibody–Drug Conjugates".