What is the optimal rodent model for anti-tumor drug testing?

One of the most serious obstacles facing investigators involved in the deve lopment and assessment of new anticancer drugs is the failure of preclinica l rodent tumor models to predict in a reliable way whether a given drug wil l have anti-tumor activity and acceptable toxicity in humans. Most previous investigations for assessing drug activity in vivo have utilized rapidly g rowing non-metastatic transplantable mouse or human tumors injected ectopic ally in syngeneic or nude mice, respectively. Some of the reasons for the i nadequacy of such models are well known and, as a result, there has been a gradual movement toward the use of transgenic oncomouse models for anti-can cer drug testing. It is too early to conclude, one way or the other, whethe r these will be superior to transplantable tumor models. Moreover, such tra nsgenic models have a number of limitations which are not widely appreciate d. It is argued that transplantable tumor models, with various modification s, might be made significantly more predictive than current models, and wou ld thus constitute a more economic alternative to the use of large numbers of transgenic oncomice. These modifications include the use of slower growi ng and genetically tagged (e.g. LacZ or GFP) tumors which are transplanted initially into orthotopic organ sites. These methods would facilitate the g rowth and detection of distant microscopic and macroscopic metastases, the response of which to anti-cancer drugs, using 'clinically equivalent doses, ' could be evaluated.