The development of metastasis is a universally grave development for cancer patients irrespective of specific cancer histology. Emblematic of this clinical problem is the biology associated with progression in osteosarcoma. Indeed, for both human andcanine cancer patients afflicted with osteosarcoma, the most common primary tumor of bone, metastasis to the lungs is the most common cause of death. Lung metastases develop in these patients despite highly effective treatment of the primary tumor. Improving our understanding of the biology of metastasis is needed to improve outcomes for these patients. It is important to emphasize that the study of metastasis must include two distinct biologic entities that are both referred to as metastasis. First metastasis is a verb that describes the process of cancer progression from a primary tumor site to a distant secondary site. Second metastasis also refers to the actual metastatic lesion that exists at the secondary site and is responsible for patient mortality. Progress towards understanding metastatic disease (both the verb and noun) and its inherent resistance to conventional treatments is limited by many factors. First, the process of metastasis is believed to begin very early in the course of diseaseprogression and has occurred in most patients at the time of their initial presentation. This provides limited opportunities to study these events in human patients alone. Second, the genetic aberrations that are responsible for the development of metastasis are complex, heterogeneous, and difficult to distinguish from the events responsible for the actual development of cancer. Finally, the access to well described patient samples is limited and often is available only after treatment with cytotoxic chemotherapy. For relatively rare human cancers such as osteosarcoma, these problems become quickly amplified.
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