Saturday, April 25, 2009

carcinogenesis revisited...,

The Scientist | Fifteen years ago, John Dick, a molecular biologist at the University of Toronto, discovered that not all cancer cells are created equal. Specifically, he showed that only a small population of self-renewing leukemia cells could create tumors, dubbing these cancer stem cells (CSCs). So, scientists asked: Can we wipe out cancer by targeting just these few rogue cells?

The model really took off in 2003 when Michael Clarke, Max Wicha, Sean Morrison, and their colleagues at the University of Michigan discovered CSCs in breast cancer—the first evidence of the cancerous supervillains in a solid tumor. Since then, CSCs have been reported in various other human tumors, including brain, lung, colon, and pancreatic cancers. "You practically can't pick up a major science journal now without seeing an article about cancer stem cells," says Wicha.

In 2007, the CSC hypothesis was thrown for a loop, however, after a team led by Kornelia Polyak, of the Harvard Medical School and Dana-Farber Cancer Institute in Boston, probed a bit deeper into the Michigan team's findings. In this month's Hot Paper, Polyak's team compared the genetic profiles of the putative breast CSCs with other more differentiated cells, and found several genetic differences between the two cell populations. This "raises doubts about whether they are direct descendents of one another," says Polyak.

The findings imply that cancer cells are moving targets, Polyak argues, which is more in line with the "clonal evolution" model of tumor generation—the long-standing idea that normal cells mutate to become cancerous, and abnormal descendants transform again, creating a mass of competing, genetically-varied cancer cells. Thus, eliminating the so-called CSCs might not be sufficient to halt cancer dead in its tracks, because the remaining cells might be able to fuel tumor growth and develop drug resistance, too.

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