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Stem Cells: The Real Culprits in Cancer? [Preview]

A dark side of stem cells--their potential to turn malignant--is at the root of a handful of cancers and may be the cause of many more. Eliminating the disease could depend on tracking down and destroying these elusive killer cells

After more than 30 years of declared war on cancer, a few important victories can be claimed, such as 85 percent survival rates for some childhood cancers whose diagnoses once represented a death sentence. In other malignancies, new drugs are able to at least hold the disease at bay, making it a condition with which a patient can live. In 2001, for example, Gleevec was approved for the treatment of chronic myelogenous leukemia (CML). The drug has been a huge clinical success, and many patients are now in remission following treatment with Gleevec. But evidence strongly suggests that these patients are not truly cured, because a reservoir of malignant cells responsible for maintaining the disease has not been eradicated.

Conventional wisdom has long held that any tumor cell remaining in the body could potentially reignite the disease. Current treatments therefore focus on killing the greatest number of cancer cells. Successes with this approach are still very much hit-or-miss, however, and for patients with advanced cases of the most common solid-tumor malignancies, the prognosis remains poor.

Moreover, in CML and a few other cancers it is now clear that only a tiny percentage of tumor cells have the power to produce new cancerous tissue and that targeting these specific cells for destruction may be a far more effective way to eliminate the disease. Because they are the engines driving the growth of new cancer cells and are very probably the origin of the malignancy itself, these cells are called cancer stem cells. But they are also quite literally believed to have once been normal stem cells or their immature offspring that have undergone a malignant transformation.

This idea—that a small population of malignant stem cells can cause cancer—is far from new. Stem cell research is considered to have begun in earnest with studies during the 1950s and 1960s of solid tumors and blood malignancies. Many basic principles of healthy tissue genesis and development were revealed by these observations of what happens when the normal processes derail.

Today the study of stem cells is shedding light on cancer research. Scientists have filled in considerable detail over the past 50 years about mechanisms regulating the behavior of normal stem cells and the cellular progeny to which they give rise. These fresh insights, in turn, have led to the discovery of similar hierarchies among cancer cells within a tumor, providing strong support for the theory that rogue stemlike cells are at the root of many cancers. Successfully targeting these cancer stem cells for eradication therefore requires a better understanding of how a good stem cell could go bad in the first place.

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