In the U.S. NCI retrospective (2001), activity in at least 33% of models of a variety of histologies predicted for clinical activity in some disease. In the NCI of Canada retrospective (2003), generally similar conclusions were reached. It should be cautioned, however, that the drugs used in these studies were for the most part 'classic' cytotoxics. Whether 'targeted' therapeutics, such as signal transduction inhibitors, antiangiogenic, or stroma-modifying agents, would perform better or worse remains to be defined.
|
Even when drugs with evidence of anticancer activity in preclinical in vivo models are given at their maximum tolerated doses, they frequently fail to produce useful activity in humans.
|
In summary, mouse xenograft models should not be viewed as ideal models for cancer drug development. Altered, nonhuman host stroma, poor predictive value when applied in an empirical sense, and questionable relation to the naturally occurring human disease are but a few features, which temper enthusiasm for their use.
|