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Despite improvements in cancer detection and therapy, metastatic disease is largely incurable. Recent research indicates that tumor cells disseminate widely early in the process of pathogenesis, and that the survival and proliferation of these cells--and thus the development of metastases--depend on interactions between the disseminated cells and their particular microenvironment. Proliferative signals and the inhibition of proapoptotic responses are both critically involved in the development of clinically significant metastases. Identification of the underlying signaling cascades may provide additional targets for antimetastatic therapy.