Sep 2013
Norman Iscove

Quietly opening up a new frontier to fight cancer

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Just a few weeks ago, when most of us were focused on soaking up the last rays of summer sun, a new development in how stem cells renew themselves didn’t see much light of day, media-wise. It should have.

Dr. Norman Iscove, a senior scientist at the Princess Margaret Cancer Centre whose pedigree traces back to pioneering bone marrow transplant efforts led by Dr. Ernest McCulloch in 1970, has quietly opened up a new frontier. One that has huge implications for cancer.

After years of work, the lion’s share of which was done by postdoctoral fellow Dr. Catherine Frelin, Dr. Iscove’s team was able to show that a gene called GATA3 plays a key role in the rate at which blood stem cells renew themselves.  They found that by tinkering with it they could get stem cells to up their self-renewal rate and make many more stem cells.

In a practical sense, this discovery could help address the shortage of stem cells for transplantation. If, by interfering with GATA3, scientists could ramp up stem cell production, doctors could then do more bone marrow transplants and save more lives.

That kind of application, however, is likely a long way off. The GATA3 findings, published in Nature Immunology, are based on work with mice – not people. “I can’t even begin to predict it,” says Dr. Iscove.  “Before knowing whether it’s playing the same role in human stem cell self-renewal, it’s too soon to say.”

But there is something more fundamental to consider here. Something that has much larger implications down the road.

“We know that stem cells can be preprogrammed in terms of longevity,” says Dr. Iscove. “There are stem cells we can purify completely that will reconstitute almost permanently. But there are others that sometime after eight weeks will begin to fail and the grafts will regress. Both of them are genuine stem cells. Both of them are capable of pumping out billions of cells every day. But one is preprogrammed to quit.  We now think that GATA3 is a key player in reprogramming the permanent stem cell to become a transient stem cell.”

Dr. Iscove believes that understanding the differences between permanent and transient stem cells is absolutely central to understanding how cancer develops.

“Cancer cells have permanence in terms of growth,” he says. “They don’t quit. They keep going. That’s why they’re dangerous.”

Viewed this way, the potential application of the GATA3 discovery is far beyond simply improving the ability to scale up the production of progenitor cells. It could be the key to shutting down cancer stem cells.

“It’s part of the puzzle of understanding permanence in stem cell renewal,” says Dr. Iscove. “How is that done and how do you break it?” The answer won’t be found anytime soon.

As said, Dr. Iscove has opened up a frontier. He and others must now explore it.

That, at the very least, is exciting.

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