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Preclinical evaluation and phase I trials

  • Chapter
The Search for New Anticancer Drugs

Part of the book series: Cancer Biology and Medicine ((CABM,volume 3))

Abstract

The discovery of new anticancer agents has occurred, variously, by a mixture of screening, analogue development, rational design and serendipity. Until quite recently, the majority of potential new agents were tested initially in vivo in mice against rapidly growing leukaemias, such as the P388 and L1210. However, experience with the National Cancer Institute, USA (NCI) in vivo tumour panel as a screening tool has been relatively disappointing because the majority of agents thus identified are inactive against slowly growing solid tumours1. The major challenge for the development of new treatments for cancer is to identify new agents with activity against the common solid tumours, such as colon and non-small-cell lung cancer (NSCLC). This has led to the establishment at NCI of an in vitro testing system based on human tumour cell lines2. While the predictive ability of this model is unknown, it is demonstrating the ability to confirm the pattern of activity of established drugs3. Moreover, there have been some examples of new compounds which exhibit tissue-determined selectivity and unusual patterns of cytotoxicity. Nevertheless, in vitro screens, as currently employed, are ill-designed to demonstrate activity with drugs which require metabolic activation, drugs acting via the immune system and drugs with bell-shaped dose-response curves. A more detailed discussion of in vitro testing is to be found in Chapter 3.

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Authors
  1. I. R. Judson
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Editors and Affiliations

  1. University of Cambridge, UK

    M. J. Waring (Reader in Chemotherapy) (Reader in Chemotherapy)

  2. CRC Human Cancer Genetics Research Group, Department of Pathology, University of Cambridge, UK

    B. A. J. Ponder (Director) (Director)

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© 1992 Kluwer Academic Publishers

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Judson, I.R. (1992). Preclinical evaluation and phase I trials. In: Waring, M.J., Ponder, B.A.J. (eds) The Search for New Anticancer Drugs. Cancer Biology and Medicine, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-0385-2_8

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  • DOI: https://doi.org/10.1007/978-94-009-0385-2_8

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6659-4

  • Online ISBN: 978-94-009-0385-2

  • eBook Packages: Springer Book Archive

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