Metastatic disease: a drug discovery perspective.

Abstract Disseminated tumor cells are present in many patients at diagnosis. At a time when the disseminated disease becomes prominent, patients have already been treated with many cycles of therapy to which their metastases were also exposed. These metastases have genetically evolved from primary tumors. Furthermore, their interaction with the tissue microenvironment plays an important role in all phases of disease development. These facts have only partially been taken into consideration when profiling anti-cancer compounds foreseen to treat patients with disseminated metastatic disease. In this perspective, we discuss the unique features of metastatic disease and review the model systems available for drug profiling. Based on an analysis of how compounds are profiled today in pre-clinical models of metastatic disease and what would be desirable and possible with the present know-how, we recommend a refined profiling process to validate drugs with potential to treat patients with overt metastatic disease.