Preclinical Cancer Therapeutics 2007

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Publication Date: 2006-11-01

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Overview

The stakes are high in the global oncology market, currently estimated at US$42 billion. Hundreds of novel and next-generation anticancer products are in research and development; however, not all are destined for market success and an estimated 37% or more key preclinical candidates may fail due to poor clinical performance despite increasing investment. The challenges for cancer research and drug development are many, but a number of strategies are proving advantageous in respect to the development of some promising oncology therapeutics.

Preclinical Cancer Therapeutics 2007: Decoding Next Generation Drug Targets for Market Success is a unique and unrivalled 367-page report analysing the performance of numerous important early stage oncology drug candidates, assessing their market viability based on preclinical scientific studies and expert opinion. In the report, analysts decode the necessary parameters of market success for novel and next-generation drug targets. Through their diligent market research and academic insight, founded on years of experience of directing a preclinical research facility for the assessment of drug targets for solid tumours, the authors identify which oncology classes and products are most suited for regulatory approval and commercial success from those that may not fare as well in the global marketplace. The report represents an essential intelligence tool for deciphering capital risk and investment in oncology therapeutics whilst also enabling important decision-making with regard to research and development programmes and strategies, regulatory issues, and marketing challenges. Furthermore, market estimations for drug classes are provided revealing those preclinical and clinical phase compounds that are most likely to succeed in the market and become high-revenue therapeutics for their developers.

Report Highlights and Key Findings

Critical analyses of the current challenges to the development of successful therapeutics approaches to the most common forms of human cancer

A comprehensive examination of which investigational oncology products are most likely to enter the market in the near future based on preclinical performance

An unrivalled in-depth overview of what major innovative therapeutic approaches to the treatment of cancer are currently in preclinical research and development

An assessment of the therapeutic insights associated with the successful introducting of targeted therapeutics such as Gleevec

Critical overview of which preclinical approaches to cancer therapeutics are likely to produce broad spectrum therapeutic applications

Focused assessment of the most relevant genes for the development of targeted therapeutics with the greatest likelihood of clinical efficacy

Table of Contents
CHAPTER 1. PRECLINICAL CHALLENGES IN THE DEVELOPMENT OF NEW PHARMACOLOGICAL AGENTS TO TREAT CANCER
CHAPTER 2. TOOLS FOR PRECLINICALDRUG DEVELOPMENT
CHAPTER 3. CANCER IMMUNOTHERAPY
Cancer Therapeutics
to Cancer
CHAPTER 4. TARGETED CANCER THERAPEUTICS: SMALLMOLECULE INHIBITORS IN PRECLINICAL DEVELOPMENT
CHAPTER 5. HORMONAL AGENTS AS THERAPEUTIC ONCOLOGYTARGETS
CHAPTER 6. PRECLINICAL ANGIOGENIC CANCER TARGETS
CHAPTER 7. PRECLINICAL PROSPECTS FOR HAEMATOPOIETIC CANCERS
CHAPTER 8. PRECLINICAL APPROACHES TO THE TREATMENT OF SOLID TUMOUR MALIGNANCIES
CHAPTER 9. MARKET OUTLOOK FOR THE MOST PROMISING ANTICANCER DRUGS CURRENTLY IN PRECLINICAL/EARLY STAGE CLINICAL DEVELOPMENT
LIST OF TABLES
Table 1.1 Oncogenes and the Types of Cancers Resulting from Their Activation
Table 1.2 Tumour Suppressor Genes and Cancers that Result from Their Inactivation
Table 1.3 Oncogenes and Tumour Suppressor Genes and the Various Proteins Encoded
Table 2.1 Most Common Preclinical Endpoints Used to Assess Therapeutic Efficacy and Safety
Table 2.2 Comparative Assessment of Imaging Modalities Used to Evaluate In Vivo Pre-clinical Tumour Responses.
Table 3.1 Summary of Individualised Therapeutic Cancer Vaccines in Preclinical/Early Stage
Clinical Development
Table 3.2 Tumour Antigen Targets in Preclinical Development
Table 3.3 Genetically Engineered Therapeutic Viruses in Preclinical Development
Table 4.1 Small Molecule Pathway Targeted Inhibitors in Development
Table 5.1 Effects of Selective Oestrogen Receptor Modulators (SERMs) on Various Tissue Types
Table 5.2 Tissues that Express Oestrogen Receptor
Table 5.3 Androgens: Sites of Production and Functions
Table 5.4 Summary of Best Potential Approaches to Steroid Receptor Mediated Malignant
Diseases
Table 5.5 Key Advantages and Disadvantages of Oestrogen Receptors as Chemotherapeutic Targets
Table 5.6 Key Advantages and Disadvantages of Androgen Receptors as Chemotherapeutic Targets
Table 5.7 Key Advantages and Disadvantages of Retinoid X Receptors and Peroxisome
Proliferator Activator Receptors as Chemotherapeutic Targets
Table 5.8 Key Advantages and Disadvantages of Progesterone Receptors as Chemotherapeutic Targets
Table 6.1 Key Physiological Events in the Activation and Resolution Phases of Angiogenesis
Table 6.2 Positive and Negative Regulators of Angiogenesis
Table 6.3 Summary of Preclinical Anticancer Agents by Drug Targets
Table 6.4 Summary of Preclinical Anticancer Agents by Mechanism(s) of Action
Table 7.1 Subtypes of Acute Myeloid Leukaemia
Table 7.2 Revised European and American Lymphoma (REAL) Classification of Leukaemias and Lymphomas
Table 7.3 Genes Implicated in Human Leukaemias
Table 7.4 Genes Implicated in Acute Myeloid Leukaemia: Potential Therapeutic Targets for Preclinical Development
Table 7.5 Genes Identified in Acute Lymphoblastic Leukaemia: Potential Therapeutic Targets for Preclinical Development
Table 7.6 Genes Identified in Chronic Lymphocytic Leukaemia: Potential Therapeutic Targets for Preclinical Development
Table 7.7 Genes Identified in NonHodgkinâ€™s Lymphoma: Potential Therapeutic Targets for Preclinical Development
Table 7.8 Novel Therapeutic Agents in Development for Acute Myeloid Leukaemia
Table 7.9 Promising Therapeutic Agents for Chronic Myeloid Leukaemia in Development
Table 7.10 Novel Therapeutic Agents for Acute and Chronic Lymphocytic Leukaemia in Development
Table 7.11 Novel Treatment Approaches in Development with Broad Spectrum Anti-Leukaemic Activity
Table 7.12 Promising New Treatment Approaches in Development for Lymphoma
Table 7.13 Promising Therapeutic Agents for the Treatment of Haematological Malignancies in Preclinical Development
Table 8.1 Promising Agents with Broad Spectrum Therapeutic Applications in Preclinical/
Early Clinical Stage Development
Table 8.2 Important Recently Identified Genes Implicated in Solid Tumour Malignancies
Table 8.3 Major Preclinical Developments in Brain Cancer Therapeutics
Table 8.4 Major Preclinical Developments in Breast Cancer Therapeutics
Table 8.5 Major Preclinical Developments in Colon Cancer Therapeutics
Table 8.6 Major Preclinical Developments in Lung Cancer Therapeutics
Table 8.7 Major Preclinical Developments in Melanoma Therapeutics
Table 8.8 Major Preclinical Developments in Ovarian Cancer Therapeutics
Table 8.9 Major Preclinical Developments in Prostate Cancer Therapeutics
Table 8.10 Promising Agents in Preclinal Development for the Treatment of Solid Tumour Malignancies
Table 9.1 Global Portfolio Revenues and Market Share of Cancer Drugs, 2005 (US$m)
Table 9.2 Summary of Promising Cancer Therapeutics in Preclinical Development by Drug Class
Table 9.3 Summary of Promising Cancer Therapeutics in Phase-I Trials by Drug Class
Table 9.4 Summary of Promising Cancer Therapeutics in Phase-II/II Trials by Drug Class
Table 9.5 Summary of Promising Novel Combination Chemotherapy Approaches in Clinical Trials
LIST OF FIGURES
Figure 1.1 The Cell Cycle
Figure 1.2 DNA Binding Agents used as Chemotherapeutic Interventions in Cancer
Figure 1.3 Growth Factors that Activate Angiogenesis
Figure 1.4 Immunological Agents
Figure 2.1 General Approach to New Drug Development
Figure 2.2 General Approaches to Drug Discovery: Random Versus Rational Drug Design
Figure 2.3 General Categories of Biotechnology Tools Used in Targeted Drug Discovery
Figure 2.4 General Categories of Drug Discovery Tools Used in Targeted Versus Non-Targeted Approaches
Figure 2.5 General Categories of Preclinical Assessment Parameters
Figure 2.6 In Vitro and In Vivo Preclinical Therapeutic Assessment Models
Figure 2.7 Goals of Preclinical Drug Discovery and Assessment Protocols
Figure 3.1 General Areas of Preclinical Cancer Immunotherapy Research
Figure 3.2 Summary of Active Immunotherapy Approaches
Figure 3.3 General Strategy for Producing Recombinant Therapeutic Viral Vaccines
Figure 3.4 Summary of Passive Immunotherapy Approaches to Cancer
Figure 3.5 Construction of Human Monoclonal Antibodies Using the Method of Phage Display
Figure 4.1 General Cell Pathways that Contain Oncogenic Targets for Small Molecule Therapeutic Inhibitors
Figure 4.2. Key Elements in PTEN/PI3K/Akt Signal Transduction Pathway
Figure 4.3 Key Elements in the Ras/Raf/Mek/ERK Signal Transduction Cascade
Figure 4.4 Key Elements of the Wnt/APC/Beta-Catenin Signal Transduction Pathway
Figure 5.1 Steroid Derivatives of Cholesterol
Figure 5.2 Receptors of the Steroid Superfamily Associated with Malignant Diseases
Figure 5.3 Intermediates in the Androgen-Oestrogen Conversion Pathway
Figure 5.4 Intermediates in the Cholesterol-Progesterone Pathway
Figure 6.1 Pro-Angiogenic Molecules Implicated in Cancer Biology
Figure 6.2 Endogenous Angiogenesis Inhibitors Derived from Matrix
Figure 6.3 Endogenous Angiogenesis Inhibitors of Nonmatrix Origin
Figure 6.4 Key Steps in the Conversion of Plasminogen to Angiostatin
Figure 8.1 General Biological Parameters of Solid Tumours Relevant to Therapeutic Design
Figure 9.1 Drug Development Parameters Critical to Market Success
Figure 9.2 Growth Rates of Best-Selling Cancer Drugs, 2005
Figure 9.3 Best-Selling Cancer Drugs, 2005 (US$m)
Figure 9.4 Market Share of the Top 10 Cancer Drugs, 2005 & 2010
Figure 9.5 Leading Oncology Companies by Chemotherapy Portfolio Revenues, 2005 (US$m)

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Preclinical Cancer Therapeutics 2007

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