Stem Cells: Hidden Key to Growth of Tumors?

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Stem cells have become famous for their ability to heal, spurring hopes that they might one day cure Parkinson's disease, spinal cord injuries and a wide variety of ailments. But now a growing number of researchers are concluding that stem cells are also the hidden force behind one of nature's most feared killers:

Cancer

Within each tumor, they believe, lurks a small population of elusive, highly potent cells that drive the tumor's growth. Under a microscope they appear identical to other cancer cells, but these cancer stem cells hold the power to produce cancerous tumors in much the same way that normal stem cells are able to regenerate the body's healthy tissues. They also seem to resist common cancer drugs, explaining why some patients can be seemingly cured of some cancers only to see the disease make a comeback.

In the past two years, cancer stem cells have gone from a theory on the fringes of biology to an idea that is attracting money and talent in cancer research. Last year a scientist at the University of Michigan announced the discovery of stem cells in breast tumors.

In the past few months, a form of leukemia and two types of brain cancer were both linked to cancer stem cells, and scientists familiar with unpublished studies said more cancers were likely to follow.

The first test in patients of a therapy targeting these stem cells is now getting under way. The discovery of cancer stem cells provides a promising new target for the war on cancer, and it could also force a profound change in cancer research, say the theory's growing number of advocates. Most treatments today are judged by their ability to shrink tumors, but the new results suggest the size of the tumor is all but irrelevant: If doctors can kill the stem cells, the tumor is doomed, but if the stem cells survive, it will be back.

Scientists caution that the path ahead will be challenging. Simply finding cancer stem cells is difficult, requiring laborious trial-and-error experiments in which biologists analyse similar, looking cancer cells for the chemical signatures of a stem cell. They then attempt to sift out those cells and see if they cause new cancers to grow. But there are lingering obstacles: Even for many healthy tissues, for instance, there is not yet a definitive test to distinguish stem cells.

Researchers are massing forces to attack the problem. This year, the Nationa1 Cancer Institute has identified cancer stem cells as one of the most important new ideas in cancer research, and next year it plans to announce a stem-cell initiative, said Allan Mufson, chief of the Cancer Immunology/Hematology Branch at the institute.

In part, the excitement surrounding the idea has come from the growing realisation that there are deep connections between the biology of cancer - perhaps the top target of biomedical research over the last three decades - and the rapidly expanding science of stem cells. Researchers say progress in understanding the origins of cancer may also give them tools to unleash the potential of stem cells for healing.

The idea also exerts a powerful emotional pull on doctors who specialise in cancer treatment because it relates directly to one of the cruelest aspects of the disease. Patients can endure surgery, radiation, and near-lethal drugs to fight their tumors, only to watch helplessly as the cancer comes raging back.

Scientists have suspected a link between stem cells and cancer cells for decades. Stem cells, which appear in many tissues in the adult body - from the skin to the blood to the brain - are unique because they have the ability to create large numbers of other cells. Scientists also sometimes refer to stem cells as "immortal" for their unique ability to renew their own ranks, seemingly indefinitely. Cancer cells seem to share some of these qualities, but they are riddled with genetic defects that make them grow into dangerous, uncontrolled masses.

The brain research, led by Dr. Peter Dirks of the University of Toronto and the Hospital for Sick Children in Toronto, looked at cells taken from human brain tumors and identified possible cancer stem cells among them: Dirks showed that as few as 140 of these cells could create an aggressive brain cancer in a mouse: But without these stem cells, even a massive dose of up to 100,000 cancer cells did not spark a cancer, according to the paper.

With other cancer scientists now, starting to direct their research toward stem cells and new findings bolstering the idea, Clarke said he now receives almost daily invitations to give presentations around the country.

Although the field has only begun to yield useful findings, scientists are already looking for ways to use this knowledge to treat cancer. They believe the key is to home in on the ways in which stem cells differ from normal cells. Radiation and traditional chemotherapy drugs tend to target cells that are dividing quickly and creating large numbers of new cells. Because this rapid division is the trademark of an active cancer, these treatments are generally effective at shrinking tumours.

Stem cells, by contrast, are usually slow to divide. When a stem cell does divide, it can create long-lived copies of itself, thus ensuring its "immortality" But a stem cell can also create progenitor cells with the power to create a group of new cells that quickly expand in number. Cancer therapies that kill only these quickly dividing cells may appear successful in the short term but leave the more important stem cells unharmed.

The search for drugs that would specifically target cancer stem cells is under way. Craig Jordan, a scientist at the University of Rochester School of Medicine and Dentistry, has been working for years with the cancer stem cells identified in 1994, looking for ways to kill them without hurting normal cells.

Two years ago, while still a researcher at the University of Kentucky, he identified a pair of drugs that targeted leukemia stem cells: Recruiting began last month for a trial in Kentucky for people who have relapsed, which is very common, and for other patients who cannot handle the toxicity of the traditional treatment.

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