Experimental models of bone metastasis: Opportunities for the study of cancer dormancy

Skeletal metastasis is prevalent in many cancers, and has been the subject of intense research, yielding innovative models to study the multiple stages of metastasis. It is now evident that, in the early stages of metastatic spread, disseminated tumour cells in the bone undergo an extended period of growth arrest in response to the microenvironment, a phenomenon known as "dormancy". Dormancy has been implicated with drug resistance, while enforced dormancy has also been seen as a radical method to control cancer, and engineering of dormant states has emerged as a novel clinical strategy. Understanding of the subject, however, is limited by the availability of models to describe early stages of metastatic spread. This mini-review provides a summary of experimental models currently being used in the study of bone metastasis and the applications of these models in the study of dormancy. Current research in developing improved models is described, leading to a discussion of challenges involved in future developments.