Dissecting the metastatic cascade

Key Points In some solid tumours, such as those of the head and neck, the presence of lymph-node metastases is closely linked to the development of distant metastases. In others, such as breast cancer, this association is less pronounced. Gene-expression profiling studies of breast cancer cells indicate that specific molecular pathways are associated with haematogenous dissemination of primary tumour cells, whereas these pathways were not involved with lymphatic dissemination. Disseminated tumour cells found in the bone marrow of patients with various types of solid tumours (for example, breast, colon and lung tumours) can be detected by sensitive immunocytochemical and molecular assays. The presence of disseminated tumour cells in bone marrow predicts the development of overt metastases — both in the bone and other organs. The genetic characterization of single disseminated tumour cells isolated from the bone marrow, along with gene-expression profiling studies of primary tumour cells, indicate that haematogenous dissemination is often a very early event in tumour progression. The cells seem to first disseminate from the early primary lesions and then acquire additional genetic defects. Single disseminated tumour cells in the blood and bone marrow are targets for adjuvant therapy. These cells often show different properties to cells of the primary tumour, so further molecular analysis will provide additional information and will help to develop antimetastatic therapies. Despite recent progress in gene-expression profiling studies, the biology underlying the various patterns of metastasis that are observed in different tumour types remains unclear. The detection and characterization of disseminated tumour cells in patients with cancer has provided important new information about the cascade of metastatic events. This information has important implications for cancer prognosis and for therapy.