It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.

Preface The ‘Seed and Soil’ hypothesis for metastasis sets forth the concept that a nutritive microenvironment, or niche, is required for disseminating tumour cells to engraft distant sites. This Opinion presents emerging data that support this concept and outlines the potential mechanism and temporal sequence by which changes in tissues distant from the primary tumour occur. To enable improvements in the prognosis of advanced malignancy, early interventions that target both the disseminating seed and the metastatic soil are likely to be required.

Eltrombopag increased platelet counts in a dose-dependent manner in patients with relapsed or refractory ITP. (ClinicalTrials.gov number, NCT00102739.)