The therapeutic response of human tumour xenografts

Abstract

The bulk of experimental therapeutic research on cancer has largely been performed on transplanted tumours in mice and other rodents. Surprisingly little attention has been given to the criteria for choosing one tumour type rather than another for a particular study. In the case of cancer chemotherapy the evidence is that substantial differences exist in the sensitivity of different cell types to a particular cytotoxic agent, and this fact influences the choice of experimental tumours that should be used. To use a highly chemosensitive lymphoid tumour as a model for clinically unresponsive non-lymphoid tumours would appear unreasonable. It is the difficulty of choosing a murine tumour system as a model for the chemotherapy of human cancer that has encouraged the use of human tumour xenografts for such work: there is the as yet unproven possibility that a xenograft maintains to a large degree the chemosensitivity of the tumour in its original host. If this is so, then such xenografts should have great advantages over murine tumours for cancer chemotherapy. There are, however, two potential drawbacks to the use of xenografts which could counteract their advantages. The first is the fact that human tumours in some respects change their biological properties on xenografting and this could lead to a change of chemosensitivity. The second is that xenografts probably grow in the face of a substantial host response that could complicate the assessment of chemosensitivity and lead to misleading results. These possible drawbacks cannot easily be dismissed.