Stem Cells That Kill

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It's easy to see why. More than 30 years after the War on Cancer was declared, malignancies in all parts of the body are still managing to evade the best therapies thrown at them. For some leukemias, survival rates have not budged since the 1970s. To be sure, there are gentler and more sophisticated forms of chemotherapy and radiation, as well as clever new drugs like Gleevec and Herceptin that take better aim at cancerous cells. But those therapies treat all cancer cells as equals. The next generation of treatments, doctors say, needs to recognize and target the root cause of tumors. "It requires a reorientation in people's thinking," says Weinberg. "We need to focus on wiping out the stem cells rather than eradicating the bulk of the tumor."

Such a shift in thinking is already under way, thanks to the special nature of cancer stem cells. Unlike embryonic stem cells, which stir up moral and political passions because they can, in theory, be used to create an entire human being, cancer stem cells are mutated forms of adult stem cells that can only make copies of their own cell type, be it blood or skin or lung tissue. What gives those adult cells their "stemness" is the ability to generate more stem cells like themselves (and thus continue to regenerate blood or skin tissue) and to churn out new generations of progeny to replace the cells that mature and die off.

The idea that the same process could be at work in cancer originated with leukemia researchers. In a series of studies in the 1990s, scientists began taking leukemia cells from human patients, separating out fractions of those cells and putting them into mice specially bred to tolerate human implants. Some of the cell fractions developed into tumors in the animals, while others did not. That was the first proof that the cells in a cancer were not homogeneous. Some cells were more dangerous than others.

The challenge is to find a way to identify and isolate those cells. Scientists are starting with what they know, analyzing the proteins that stud the surface of normal stem cells and looking for proteins unique to the cancerous cells. So far, leukemia experts have the edge, working from the knowledge of blood stem cells they have been building since the 1940s. Dick's group in Toronto was the first to identify a protein, CD34, as a potential screen for leukemia stem cells. He showed that tumor cells with plenty of CD34, when injected into mice, flowered into cancerous growths. Leukemia cells without the protein, by contrast, did nothing.

The hope is that once those "stem-defining" proteins are identified, they might be used as targets for drug therapies that could lead to better cancer treatments. Irv Weissman, the developmental biologist at Stanford University who first isolated the blood-forming stem cell, is working on pinpointing just such a suite of proteins for leukemia.