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Stem cells core of more cancers

New discoveries that pinpoint bad seeds leading to a major redirection of research

From Monday's Globe and Mail

A spate of new discoveries about the basic biology of cancer is pushing researchers toward an astonishing conclusion: For decades, efforts to cure the disease may have targeted the wrong cells.

Current therapies treat all cancer cells the same. They're aimed at shrinking tumours on the basis that the various cells within them all have similar powers to spawn new cancers and spread destruction.

But mounting evidence suggests that cancer's real culprits -- the roots of perhaps every tumour -- are actually a small subset of bad seeds known best to the world as stem cells.

"It is not unreasonable to say that all this time, the 30 or 40 years that chemotherapy and radiation [have] been around, we've been going after the wrong cells," said Alan Bernstein, president of the Canadian Institutes of Health Research, the country's main medical research funding agency. If the theory bears out, he said, "All of our therapies have been targeting and killing the pawns.

"But like chess, you have to kill the king to win the game."

Abnormal stem cells have now been identified as the engines driving certain cancers of the blood, breast, brain, bone and prostate. And today, two research groups -- one in Canada and another in Italy -- report in an advance online publication of the journal Nature that they have pinpointed aberrant stem cells as the source of colon cancer, the second leading cause of cancer deaths.

"A lot is known about the genetics of colon cancer, but despite all our knowledge, too many people keep relapsing and dying," said John Dick, the senior scientist at the University of Toronto and Princess Margaret Hospital who led the work.

Dr. Dick, who discovered the first cancer stem cell in 1994 in leukemia, said the new work shows that while current therapies treat colon cancer as a "homogeneous entity, not every colon cancer cell has the ability to keep that tumour going; only one in 60,000."

New research has repeatedly shown that contrary to conventional wisdom, only abnormal stem cells can sprout and sustain tumours by renewing themselves indefinitely. Without signals from cancer stem cells, ordinary tumour cells seem to stop growing.

What's more, some experiments have found these bad seeds to be highly resistant to standard cancer therapies, including radiation, medicine's nuclear weapon.

The findings may explain why cancers come back even after treatments seem to make tumours disappear. Just a small number of mutant stem cells left behind -- invisible to the naked eye or any scan -- may be enough to spark cancer's regrowth.

"Killing 98 per cent of tumour cells on a scan may look good, but that 2 per cent could be enough to grow the cancer back," said Jeremy Rich, a neuro-oncologist and cancer researcher at Duke University in North Carolina. "Maybe one of the reasons we haven't been as good as we thought we could be is because we've been looking at the wrong cells."

Normal stem cells are usually cast as stars in science. Plucked from a developing embryo, they're prized as immortal chameleons with the power to multiply indefinitely and give rise to myriad tissues that make up the human body. They've become lightening rods for moral and political debate as researchers rush to explore their potential as the keys to regenerative medicine.

But only in recent years have scientists developed the means to detect them and the methods to test their function. In the process, an old theory about their more sinister side as the source of cancer has moved from fringe to forefront.

"This is the most promising advance in thinking about cancer in a very long time. This opens up brand new targets," said the CIHR's Dr. Bernstein, even if, he acknowledged, "All of our thinking about how to treat cancer needs to be rethought."

Indeed, some scientists suspect that heaps of cancer research will have to be reinterpreted -- if not redone -- in light of what has been dubbed "the cancer stem cell hypothesis."

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