How cancers cells make that journey has long puzzled researchers: the cells that make up cancers in epithelial tissue, such as the surface cells of the lung and breast, generally prefer to stick together and are not suited for a rough-and-tumble trip through the bloodstream. One theory holds that metastasizing tumour cells activate pathways that are normally reserved for ‘mesenchymal’ cells, which move around in developing embryos2. This has been termed the epithelial–mesenchymal transition, or EMT, and some companies have been hard at work developing drugs that target this switch. But most of evidence supporting a role for the EMT in cancer spread has come from animal models. And analyses of tumour cells circulating in the blood has been limited because the techniques tend to pick up only epithelial cells. “It was pioneering technology, but we’ve always been worried that if EMT was happening, we’d miss the mesenchymal tumour cells this way,” says Dive.
Daniel Haber and Shyamala Maheswaran, both at the Massachusetts General Hospital Cancer Center in Boston, and their colleagues, therefore developed a new suite of markers to identify tumour cells circulating in the blood. They then tracked these cells, and characterized their gene expression, in 11 people undergoing chemotherapy for breast cancer. The team found that when tumours responded to treatment, the proportion of circulating tumour cells harbouring mesenchymal features began to drop. Failure of therapy was followed by resurgence of mesenchymal tumour cells.