Cells get their instructions from genes, so one way of stopping the spread of cancer would be to change the signals the cells receive from the genes. David Kwiatkowski, MD, PhD, and Alan Lader, PhD, of Dana-Farber Cancer Institute in Boston have identified more than 20 genes involved in the metastatic process. They have discovered that some genes are present in greater or lesser numbers in metastatic cells than in normal cells. They are now examining these genes in detail to determine which are absolutely critical for metastasis and which might be targets for drug therapy.
Drs. Kwiatkowski and Lader have preliminary results on one gene that looks promising. However, another year or two of work in the laboratory is required before studies in animals can begin. Studies in patients are a long way down the road.
At present, no single “metastasis gene” has been identified, except for the membrane-cytoskeleton component ezrin, which appears to be necessary for metastases in rhabdomyosarcoma and osteosarcoma.
The role of chemokine receptors is another area under investigation. Chemokines are substances secreted by cells that have an effect on other cells, such as in promoting metastasis. For example, some breast cancer cells express the chemokine receptors CXCR4 and CCR7. The chemokines that bind to these receptors are very common in the parts of the body where breast cancers commonly metastasize. Studies in animals indicate that blockage of the interaction between CXCR4 and its chemokines decreases breast cancer metastases.