In vitro carcinogenicity testing: present and future perspectives in pharmaceutical development

Almost all new drugs must be tested for carcinogenicity at some point during their development, and ultimately, a lifetime in vivo assay, usually in rodents, must be performed. Many in vitro assays of carcinogenicity have been developed for use before short- or long-term in vivo testing in order to remove from the development stream those drugs that are likely to produce tumors in vivo. This review discusses in vitro assays that are required by the International Conference on Harmonization, followed by a discussion of in vitro carcinogenicity assays, which are currently in use, but are not specifically required. The concluding section is devoted to a discussion of high-throughput compatible carcinogenicity screens and potential human cell-based high-throughput compatible screens with reference to future methods in silico.