Until recently, most of the emphasis in cancer research has been on the pathogenesis of primary tumours. Most cancer deaths, however, are the result of metastatic disease. Nature Reviews Cancer has therefore devoted extra attention to metastasis in this issue. This is a tricky subject, as there is no one single defining genotype or phenotype of metastatic tumours — nor does there seem to be a defined class of researcher that works on metastasis. A number of factors determine the site to which a tumour will metastasize (discussed by Chambers et al. on page 563), and Gregory Mundy explains, on page 584, how studying the basic biology of bone has led to the identification of factors that contribute to skeletal metastases. On page 573, Kari Alitalo discusses the role of lymphangiogenesis in the metastatic process.
But what have we learned from this recent flood of information? One of the most amazing features of metastatic tumours is the degree to which they differ — genotypically and phenotypically — from their primary tumour. In fact, one of the fundamental questions about metastasis is whether these changes take place in the primary tumour, allowing it to spread to a specific secondary site, or if primary tumour cells that are carried to secondary organs undergo these changes after they are exposed to the new microenvironment. In either case, the plasticity of metastases makes them a significant therapeutic challenge.
