Orthotopic models are necessary to predict therapy of transplantable tumors in mice

Rapid evaluation of new cytotoxic agents and biological response modifiers for therapy of cancer and elucidation of their mechanisms of action require the use of relevant animal models. It is well established that the faithfu l reproduction of the tumor microenvironment that allows the emergence of s ubpopulations of tumor cells with the biological and metastatic properties observed in clinical cancer occurs with orthotopic tumor models (transplant able and transgenic). This review summarizes the evidence that phenotypic p roperties of metastatic cells are governed by the expression of genes that are regulated by interaction with the relevant organ environment. While ect opic models of cancer allow rapid screening of new compounds and transgenic models afford opportunities to study early cellular and molecular events i n tumor progression and metastasis, orthotopic transplantation of tumor cel ls remains an affordable, reproducible and reliable methodology for the stu dy of organ-specific determinants of the biology and therapy of cancer.