Crit Rev Eukaryot Gene Expr 2002 ;12(2):137-50
University of Texas M.D. Anderson Cancer Center, Department of Cancer Biology, Houston 77030, USA.
Metastatic disease, mainly to the lungs, liver, bone, and brain, is the most common cause of death from breast cancer, despite advances in surgical and clinical management. Two basic principles govern the process of metastasis. First, that tumors are heterogeneous populations of cells, and second, that the process is a sequence of events that depends on tumor cell properties and interactions with the microenvironment at the site of metastasis. Inhibitors targeted at any of these different steps have the potential to inhibit metastatic progression, and examples of key therapeutic targets include overexpression of growth factor receptors, angiogenic factors, matrix metalloproteases, and integrin receptors. The identification of molecular targets for therapy of breast cancer metastasis will be accelerated by DNA array technology, and their selection for use should include evaluation of interactions between tumor cells and normal tissue components. These sorts of inhibitors are likely to target both cancer and normal cell functions, for example, inhibitors of matrix metalloproteases that can potentially inhibit both tumor cell invasion and angiogenesis. The use of appropriate animal models will be necessary to determine the impact of targeted inhibitors on the growth and development of breast cancer metastasis.