SOME cancer cells are more equal than others 鈥� and many existing treatments fail to kill the most dangerous ones. That鈥檚 the new picture emerging from recent studies, which suggest that a small number of stem-cell-like cells within tumours give rise to all the rest of the cancerous cells.
The good news is that finding ways to target these ringleader cells should be more effective than the 鈥渒ill-鈥檈m-all鈥� approach. 鈥淲e鈥檙e quite excited. If it鈥檚 only a small number of cells maintaining cancer, today鈥檚 treatments may be failing because those particular cells aren鈥檛 being wiped out,鈥� says Peter Dirks of the University of Toronto鈥檚 Hospital for Sick Children in Canada.
It has been known for years that rogue stem cells play a role in leukaemia. Here cells within the bone marrow produce too many white blood cells 鈥� it is the excess white blood cells that kill but it is the rogue bone marrow cells that have to be killed to cure the disease.
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Solid tumours were thought to be different, with every cancerous cell dividing madly to form new cells. But recent studies suggest that 鈥渃ancer stem cells鈥� also exist in breast tumours. Last year Dirks鈥檚 team found them in brain tumours, too, and he told New 杏吧原创 that he has seen unpublished research suggesting that the same is also true of several other solid cancers. 鈥淭here are lots of people looking into it now, and we鈥檒l see lots more over the next year,鈥� he says.
In the latest study, Dirks鈥檚 team has shown that as few as 100 of the brain tumour stem cells discovered last year, which bear a surface protein called CD133, can give rise to identical tumours when injected into the brains of mice. Like the original tumours, the new tumours contain a multitude of different cell types.
Yet other cells from the same tumours that lack CD133 do not form new tumours, even if 100,000 of them are injected (Nature, vol 432, p 396). These cells do survive in the brains of the mice, but they do not grow out of control. 鈥淲e were surprised by the potency of the CD133 cells,鈥� says Dirks. 鈥淲e thought every cell in the cancer would be aggressive, but it was just those.鈥�
One problem yet to be solved is whether the CD133 cells are stem cells turned rogue, or specialised brain cells that have somehow reacquired stem-cell-like properties. 鈥淚t鈥檚 our hunch that it鈥檚 a stem cell gone bad,鈥� says Dirks.
Whichever it is, the picture emerging is that a small number of cancer stem cells drive the growth of at least some tumours. When they divide, some of the daughter cells remain as stem cells. Other daughter cells start to divide like crazy, giving rise to a range of cells that make up the bulk of the tumour 鈥� but they do not keep on dividing indefinitely. This could be why treatments designed to target actively dividing cells often fail: they may kill many secondary cells, but leave the crucial stem cells alive.
鈥淭oday鈥檚 treatments may be failing because a small number of cancer stem cells are not being wiped out鈥�
鈥淟eukaemia stem cells are almost entirely quiescent and therefore unlikely to respond to standard chemotherapy drugs,鈥� says Craig Jordan of the University of Rochester in New York, whose team is investigating ways to target these cells. Dianna Howard鈥檚 team at the University of Kentucky Chandler Medical Center has already begun a clinical trial of a treatment designed to target stem cells that cause acute myelogenous leukaemia.
Now researchers can begin trying to develop similar treatments for breast and brain cancers. And if cancer stem cells turn out to play a role in many other kinds of tumour as well, the findings could lead to a profound change in treatment strategies.
