Mouse models of metastasis: progress and prospects

Metastasis is the spread of cancer cells from a primary tumor to distant sites within the body to establish secondary tumors. Although this is an inefficient process, the consequences are devastating as metastatic disease accounts for >90% of cancer-related deaths. The formation of metastases is the result of a series of events that allow cancer cells to escape from the primary site, survive in the lymphatic system or blood vessels, extravasate and grow at distant sites. The metastatic capacity of a tumor is determined by genetic and epigenetic changes within the cancer cells as well as contributions from cells in the tumor microenvironment. Mouse models have proven to be an important tool for unraveling the complex interactions involved in the metastatic cascade and delineating its many stages. Here, we critically appraise the strengths and weaknesses of the current mouse models and highlight the recent advances that have been made using these models in our understanding of metastasis. We also discuss the use of these models for testing potential therapies and the challenges associated with the translation of these findings into the provision of new and effective treatments for cancer patients.
Summary: This Review describes the currently available mouse models of metastasis, focusing on the mechanistic and therapeutic insights that have been gained by their application, strengths and weaknesses of different models and key technological advances that are generating more refined models.