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Vascular Disruptive Agents for the Treatment of Cancer

  • Book
  • © 2010

Overview

Editors:
  1. Tim Meyer

    1. Cancer Institute, University College London, London, United Kingdom

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  • This book discusses preclinical target identification and validation, and the optimum pre-clinical animal models

  • Biomarkers and imaging modalities used to assess the efficacy of these agents are examined

  • A review of the clinical development of key drugs is provided

  • Recent research exploring rational combinations of VDAs with other agents is reviewed and the potential place of VDAs in the future of cancer therapy is critically appraised

  • Includes supplementary material: sn.pub/extras

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Table of contents (11 chapters)

  1. Front Matter

    Pages i-ix
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  2. Pre-Clinical Development

    1. Front Matter

      Pages 29-29
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  3. Development of Vascular Disrupting Agents

    1. Development of Vascular Disrupting Agents

      • Graeme J. Dougherty, David J. Chaplin
      Pages 1-27

  4. Pre-Clinical Development

    1. Front Matter

      Pages 29-29
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    2. The Discovery and Characterisation of Tumour Endothelial Markers

      • Dario Neri, Roy Bicknell
      Pages 31-48

    3. The Use of Animal Models in the Assessment of Tumour Vascular Disrupting Agents (VDAs)

      • R. Barbara Pedley, Gillian M. Tozer
      Pages 49-75

    4. Combination Therapy with Chemotherapy and VDAs

      • Giulia Taraboletti, Katiuscia Bonezzi, Raffaella Giavazzi
      Pages 77-93

    5. Lessons from Animal Imaging in Preclinical Models

      • Lesley D. McPhail, Simon P. Robinson
      Pages 95-116

    6. Combining Antiangiogenic Drugs with Vascular Disrupting Agents Rationale and Mechanisms of Action

      • Yuval Shaked, Paul Nathan, Laura G. M. Daenen, Robert S. Kerbel
      Pages 117-134

  5. Imaging in the Development of Vascular Disruptive Agents

    1. Front Matter

      Pages 135-135
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    2. MRI to Assess Vascular Disruptive Agents

      • Martin Zweifel, Anwar R. Padhani
      Pages 137-163

    3. Contrast Ultrasound in Imaging Tumor Angiogenesis

      • Grzegorz Korpanty, Rolf A. Brekken
      Pages 165-179

  6. Clinical Development

    1. Front Matter

      Pages 181-181
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    2. The Clinical Development of Tubulin Binding Vascular Disrupting Agents

      • Martin Zweifel, Gordon Rustin
      Pages 183-216

    3. ASA404 (DMXAA): New Concepts in Tumour Vascular Targeting Therapy

      • Bruce C. Baguley
      Pages 217-230

    4. Vascular Disruptive Agents in Combination with Radiotherapy

      • Henry C. Mandeville, Peter J. Hoskin
      Pages 231-250

  7. Back Matter

    Pages 251-256
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Keywords

About this book

Angiogenesis (formation of new vessels from pre-existing ones) is a crucial early event in the process of tumor development. New vessels supply the tumor with nutrients that are needed for further local growth and enable distant metastases (Folkman 1995). Judah Folkman (1971) highlighted the potential therapeutic imp- cations of tumor angiogenesis. He hypothesized that if tumor angiogenesis is inhibited, then tumor growth and metastasis will be impaired greatly or even impossible. The subsequent quest for endogenous and exogenous inhibitors of angiogenesis has yielded a variety of promising therapeutic agents that block one or more angiogenic pathways, a few of which have been approved by the FDA (e. g. , bevacizumab, sorafenib, sunitinib) for use as single agents or in combination with chemotherapy in specific populations of cancer patients (Sessa et al. 2008). There has also been a dramatic expansion in the exploration of novel anti-angiogenic agents pre-clinically and in clinical trials (Ferrara 2002). Some of the most promising data comes from the development of agents that inhibit one of the key growth factors involved in tumor angiogenesis – vascular endothelial growth factor (VEGF) (Ferrara et al. 2003). Bevacizumab is a monoclonal antibody against VEGF that was the first an- angiogenic agent that improved significantly the overall survival of patients with colorectal and non-squamous non-small cell lung cancer (Ferrara et al. 2005). Various agents that target tumor angiogenesis are currently under investigation in different cancer types in many clinical trials (Ferrara and Kerbel 2005).

Editors and Affiliations

  • Cancer Institute, University College London, London, United Kingdom

    Tim Meyer

About the editor

Dr. Tim Meyer is a Senior Lecturer in Medical Oncology at the UCL Cancer Institute in London where he specialises in gastrointestinal cancers and drug development. He trained in medicine at UCL and obtained his PhD from London University, after which he completed specialist training in medical oncology. His major research focus is antibody-based vascular targeting.

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