A Tumor's Lifeblood?

By Jessica Gorman

A Tumor's Lifeblood?

Scientists are investigating whether tumors are driven by stem cells

By Jessica Gorman

Cancer stem cells may replenish a tumor much the way a small number of adult stem cells maintain the body's tissues. "Cancer, I think, is best thought of as an abnormal organ," says Wicha.

Cancer stem cell researchers suggest that new therapies should be aimed right at the root of this aberrant organ. "Since these seem to be the cells that are driving the growth and spread of the cancer, these cells need to be eliminated," says Clarke.

"But that may be tricky," adds Peter Dirks, a neurosurgeon and scientist at the Hospital for Sick Children in Toronto, whose lab reported finding cancer stem cells in brain tumors. "These [cancer] stem cells may share some properties with the normal stem cells, so we'd have to be careful that our therapies aren't going to target the normal stem cells."

Developing drugs that kill cancer stem cells could also be hard because some cancer stem cells may divide more slowly than other cancer cells, and current drugs target rapidly dividing cells. Moreover, says Dirks, some cancer stem cells may have properties that make them inherently drug-resistant.

While investigators are searching for ways to kill cancer stem cells directly, they're also considering ways to strip them of their stem cell qualities, says Dick, whose lab reported the first cancer stem cells, in leukemia, a decade ago. If a drug could induce cancer stem cells to differentiate into more specialized cells, it may be possible to stop their endless proliferation.

And if a tumor is driven by cancer stem cells, this could have implications for metastatic cancer. According to Clarke, "these cells are really the cells that are driving the metastases that are killing people." For instance, Wicha says, when tiny amounts of cancer, called micrometastases, spread to a patient's bone marrow, it's not clear if they will grow. The ones that develop into large metastases are likely those that contain cancer stem cells, he believes. Cancer stem cells may also cause recurrences, he says, sitting dormant for years before waking up.

Clinical trial designers should reconsider the use of tumor shrinkage as a measure of whether a drug works, Wicha adds. Cancer stem cells may remain behind even if a drug destroys a significant portion of a tumor, he says.

But while the design of new therapies to target cancer stem cells is certainly a tantalizing idea, some scientists are striking a cautionary note. More basic research is needed to confirm that the cells researchers have identified as cancer stem cells are indeed cancer stem cells, says tumor biologist Richard P. Hill of the Ontario Cancer Institute/Princess Margaret Hospital in Toronto. "It looks very promising that there are cells in tumors which are stem cells," says Hill.

However, it's possible that the cells researchers have identified just have special abilities to grow in mice after transplantation, he says. A cancer cell population that grows after being transplanted wouldn't necessarily be able to promote growth at the population's original tumor site, he says. "The real issue, from the point of view of therapy, is: Can it actually re-grow at the [human] site where it's being treated? Or, if one's thinking about metastasis, could it grow at a metastatic site?"

And while normal adult stem cells maintain their stem cell qualities, Hill says, cancer cells have genetic changes, which leaves open the possibility that cancer cells might "lose or regain stem cell properties" over time.

"The proof will be in the pudding," concludes Dick. "Until somebody comes up with a therapy that truly exploits the stem cell property, and could only have generated that therapy based on knowledge of the stem cells, [cancer stem cells are] another interesting line of cancer research, of which there are many."

"But," says Dick, "my viewpoint is that there is pretty compelling evidence."  CR endbox 

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