How accurate is in vitro prediction of carcinogenicity?

Richard Maurice Walmsley, Nicholas Billinton

    Research output: Contribution to journalArticlepeer-review


    Positive genetic toxicity data suggest carcinogenic hazard, and this can stop a candidate pharmaceutical reaching the clinic. However, during the last decade, it has become clear that many non-carcinogens produce misleading positive results in one or other of the regulatory genotoxicity assays. These doubtful conclusions cost a lot of time and money, as they trigger additional testing of apparently genotoxic candidates, both in vitro and in animals, to discover whether the suggested hazard is genuine. This in turn means that clinical trials can be put on hold. This review describes the current approaches to the 'misleading positive' problem as well as efforts to reduce the use of animals in genotoxicity assessment. The following issues are then addressed: the application of genotoxicity testing screens earlier in development; the search for new or improved in vitro genotoxicity tests; proposed changes to the International Committee on Harmonisation guidance on genotoxicity testing [S2(R1)]. Together, developments in all these areas offer good prospects of a more rapid and cost-effective way to understand genetic toxicity concerns. © 2011 The British Pharmacological Society.
    Original languageEnglish
    Pages (from-to)1250-1258
    Number of pages8
    JournalBritish Journal of Pharmacology
    Issue number6
    Publication statusPublished - Mar 2011


    • GADD45a
    • genotoxicity testing
    • ICH S2
    • safety assessment
    • screening


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