Über den Autor
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.
Introduction nGraeme J. Dougherty and David J. Chaplin nnPre-clinical developmentnnThe discovery and characterisation of tumour endothelial markersnDario Neri and Roy BicknellnThe Use of Animal Models in the Assessment of Vascular Disrupting Agents nR Barbara Pedley and Gillian M TozernCombination therapy with chemotherapy and Vascular Disrupting AgentsnG. Taraboletti, K. Bonezzi and R. GiavazzinLessons from Animal Imaging in Pre-Clinical ModelsnLesley D. McPhail and Simon P. Robinson nCombining antiangiogenic drugs with vascular disrupting agents: Rationale and mechanisms of actionnYuval Shaked, Paul Nathan, Laura G. Daenen, and Robert S. KerbelnnImaging in the development of vascular disruptive agents nnMRI to assess vascular disruptive agents nAnwar Padhani and Martin ZweifelnContrast ultrasound in imaging tumor angiogenesisnGrzegorz Korpanty and Rolf A. Brekken n nClinical development nnThe Clinical Development of Tubulin Binding Vascular Disruptive AgentsnMartin Zweifel and Gordon J.S.RustinnASA404 (DMXAA): New Concepts in Tumour Vascular Targeting TherapynBruce C. Baguley nVascular disruptive agents in combination with radiotherapynHenry C. Mandeville and Peter J. Hoskin
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).
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