Among the things he has discovered from those wrongdoers: cells both start out with the capacity to metastasize and acquire it later. (Previous theories had been in the either/or category.) His team also discovered that many of the genes that support metastasis need to work in concert to achieve their goal. Activating just one or two of them doesn't do the trick. In 2003, he reported on the gene combination found in breast cancer cells that are prone to spread to the bone. More recent research by Massagué, published in 2007, has focused on four genes that regulate blood vessel growth and appear to be critical to the spread of breast cancer to the lungs.

Experiments in mice revealed that silencing these genes individually decreased tumor cells' ability to set up house in the lungs and that silencing them all basically shut the tumor down.

What's more, two drugs already on the market—Erbitux and Celebrex—can counteract the action of these genes in mouse studies. Clinical trials may begin as soon as a year from now, says Norton, who is collaborating with Massagué on this work. Meanwhile, Massagué's team has also discovered that certain microRNAs—small nucleotides that suppress gene function—are in short supply in some metastatic cells, suggesting, again, that a brake has been turned off somewhere. Adding them back to cells appears to turn off genes involved in cell proliferation and migration, neutralizing the cells' ability to spread.

“If you silence the genes with microRNA molecules, or you silence their products with drugs that work against them, you accomplish a synergistic slow down of metastasis,” Massagué says. “In the pharmaceutical armamentarium we have, there may already be many things that one can resort to while waiting the proverbial 10 to 15 years to develop a drug on a newly found target.”

Of what comes next, Massagué is circumspect. “I don't know. I'm the guy who, initially was thinking in terms of five more months,” he laughs. Then his ambition surfaces and he gets serious. “Right now we are in the thick of deconstructing genes to see how they are used in metastasis and how one can intervene. I see myself, for at least another five years, wholly pushing, painting this new canvas: metastasis.” TGF beta, he says, has recently been implicated in metastasis of breast cancer to the lung—a neat connection of his work that he intends to explore.

There are, he says, plenty of questions to be asked—and answered. Why, for example, do different types of breast cancer migrate to the same organs—but use different genes to do so? He's finally thinking about career trajectories—but maybe someone else's. “One could start a career studying metastasis in his or her thirties and retire having worked on nothing else.”

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