Orthotopic models of cancer for preclinical drug evaluation: advantages and disadvantages

Considering the enormous effort that has taken place over the years to discover new chemotherapeutic drugs for treating the common cancers, the conventional murine and xenograft test systems used to test efficacy for drug development have identified only a limited number of useful agents that are active clinically at well tolerated doses. In recent years, considerable effort has been made to develop more clinically relevant models by the use of orthotopic transplantation of tumour material in rodents. It has been shown that it is now possible to transplant tumour material from a variety of tumour types into the appropriate anatomical site and often these tumours will metastasise in a similar manner and to similar locations as the same tumour type will in human cancer. As yet, although a body of literature has amassed on the technique itself and its implications for metastasis, there are relatively few laboratories using these test systems in drug development programmes. Nevertheless, given the expertise now being developed and some interesting observations being made on the role of the tumour site on response to therapeutic agents, it is likely that the use of orthotopic systems will strengthen our ability to select the most appropriate molecules for recommended use in clinical studies. (C) 2003 Elsevier Ltd. All rights reserved.