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The impact of genomics on biomedical research and the development of efficient technology platforms allowing for highly parallel compound synthesis and screening procedures have led to a major paradigm shift in drug discovery and development. Efficient tools for the selection and validation of drug targets both at the preclinical and clinical level are required. Non-invasive imaging and in particular molecular imaging methods are becoming essential technologies to support drug discovery and dvelopment. Imaging provides structural, functional, metabolic and molecular readouts that are being applied to characterize a disease phenotype (diagnosis), to elucidate molecular mechanisms involved, to evaluate drug efficacy and safety, and to identify potential biomarkers of the drug's mechanism-of-action, efficacy and safety. Non-invasive imaging techniques constitute a bridge between preclinical and clinical drug evaluation. In this monograph the contribution of imaging modalities to the various stages of drug discovery and development, from early target validation to their use in clinical development programs, is described. Chapters are devoted to the description of the drug discovery process as such, to the various imaging modalities being used both preclinically and clinically, to applications of imaging during the optimization of a lead compound (addressing issues such as bioavailability and efficacy) and during the drug safety evaluation. A chapter describes imaging biomarkers, their development, advantages and the potential pitfalls associated with their use. In the translation of imaging tools from animals to man regulatory issues have to be addressed, which are dealt with in a separate section. The monograph provides a comprehensive overview on the role of imaging in drug discovery today and discusses major developments and trends both with regard to technologies and applications.

Physical methods for diagnosis --- radiologie --- medische beeldvorming

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There have been tremendous advances in our understanding of molecular and tumor biology during the past few years. In the field of cancer therapeutics, it is expected that cytotoxic drug approaches will be gradually replaced with treatments based on biological targeted approaches. Hopefully these new targeted therapies will significantly increase efficacy and lack the devastating and troublesome side effects elicited by cytotoxic chemotherapy. This volume is the first book to cover the general topic of targeted cancer therapy. It presents a range of targets such as tumor angiogenesis, cell cycle control and cell signalling, COX-2, apoptosis/cell survival, invasion and metastasis and approaches like kinase inhibitors, antisense, and antibody-based therapeutics. The emphasis is on preclinical development, including target validation, development of biomarkers, strategies for combination approaches, and development of resistance. The particular challenges involved in translating these data to clinical application are discussed. This volume should be of broad general interest to researchers and clinicians involved in cancer therapy as well as other scientists interested in current strategies for cancer treatment.

Molecular biology --- Oncology. Neoplasms --- oncologie --- moleculaire biologie