The Use and Refinement of Rodent Models in Anti-cancer Drug Discovery: A Review

Abstract

This review describes the changing use of tumour models in rodents (predominantly mice) as employed over the last four decades in anti-cancer drug discovery, and the refinements in the experimental methods used. Such models are required to examine the complexities of cancer biology (e.g. tumour angiogenesis, invasion and metastasis, host immunity factors) and the impact of potential therapies (e.g. drug pharmacokinetics, pharmacodynamics and therapeutic index), and they have produced efficacious human therapeutics. Animal welfare considerations have driven refinements to animal models of cancer over time, with the most dramatic refinements being facilitated by the move away from inherently cytotoxic therapeutic approaches toward targeted inhibitors of disease-related processes. Whereas, four decades ago, the impact of disease burden was used as an endpoint in the absence of defined mechanistic parameters, acute pharmacodynamic measures are now increasingly used to minimise the adverse effects of disease and experimental procedures in a given animal. The changes in the UK guidelines on the use of rodents in preclinical cancer testing are also used as an illustration of the progressive refinement in tumour models and drug testing.