Tumor Starters: Stem Cells Eyed as Anti-Cancer Target

Nov. 24, 2006 — -- Decades of cancer research may need to be re-evaluated, because standard tumor-targeting therapies may be off the mark, mounting research suggests.

Current cancer therapies attack tumors as if every cell in that tumor were the same. But now, scientific evidence suggests that only a small percentage of those tumor cells are responsible for the tumor's growth. Treatments that attack the whole tumor may be off target because they aren't designed to kill the cells at fault -- stem cells.

Called the cancer stem-cell hypothesis, it could revolutionize the way some cancers are treated, experts said.

"The cancer stem-cell theory solves several unanswered questions," said Dr. Raphael Catane, chairman of the department of oncology at Sheba Medical Center in Israel.

A Likely Culprit

Stem cells have an unbeatable potential to develop into many different cell types in the body. While an adult skin cell can duplicate only more skin cells, a stem cell's cellular future is less restricted.

But that future isn't always bright. Abnormal stem cells are responsible for cancers of the blood, breast, brain, bone and prostate, according to past research.

Now, scientists from Canada and Italy report that colon cancer is also caused by abnormal stem cells. The report appears in this week's issue of the journal Nature. The evidence keeps mounting.

Stem cells, specifically embryonic stem cells, also have an unmatched potential for generating controversy. Usually, those cells spark ethical debates about when life begins, so to speak, or whether embryonic stem cell research destroys life by using cells from discarded embryos.

Cancer stem cells are not embryonic stem cells but are derived from adult tissue. Nevertheless, it's possible that scientists may seek to use embryonic stem cells as part of their cancer stem-cell research.

Support for Stem-Cell Hypothesis

Researchers are now convinced that cancer stem cells -- which make up only a tiny fraction of a tumor -- produce the other tumor cells that make up the bulk of the cancer. The stem cells react very differently to chemotherapy drugs or other cancer treatments than the tumor cells do, said Dr. Grover Bagby, director of the Oregon Health and Sciences University Cancer Institute in Portland, Ore.

"That is, the [tumor cells] can be sensitive to an anti-cancer drug, but their stem cells can be resistant to that drug," said Bagby.

Why do drugs affect these two cell types so differently?

Some of the difference is due to how the cells grow. Tumor cells generally grow faster than normal cells. That's one of the things that makes cancer so dangerous.

"Cancer therapy to date has been focused primarily on rapidly dividing cells, relative to the body's normal, more slow-growing cells," said Dr. Marisa Weiss, president and founder of breastcancer.org.

So, fast-growing cancer cells are particularly vulnerable to cancer therapies. Stem cells, however, don't grow quickly the way cancer cells do.

"If stem cells are dormant and not growing, they usually escape damage from cancer treatment," said Weiss. "The cells manage to survive, able to cause more trouble in the future by giving rise to more cancer cells."

The existence of these cancer stem cells helps explain why tumors can so often grow back. If treatment doesn't kill the stem cells, they will just replicate to create a new tumor.

It's sort of like trying to clean up the flood from a broken faucet. Collecting the running water into a bucket might stop some of the flood, but the water won't stop running until you turn the faucet off.

Science, Industry Interest Kindled

The hypothesis isn't brand-new, but the data that supports the hypothesis is piling up, said Bagby. Both industry and academia have serious interests in and hopes for this research.

The interest is warranted. This theory could be explosive.

Studying the cancer stem-cell hypothesis could allow scientists to understand how cancers develop and why some resist treatment. Doctors may be better able to predict how anti-cancer drugs would work and how well they'd work, since they now know what their true target is within the tumor, said Catane.

Doctors and scientists may revisit and re-evaluate current theories, but that doesn't mean that today's treatments are all wrong.

Today's cancer treatments have led to many cancer cures and will undoubtedly lead to more cures. The discovery of cancer stem cells doesn't really mean that doctors have been hitting cells that aren't dangerous. It means that doctors now know they have another cellular enemy to watch out for.

"Our ability to eliminate all cancer does depend on the elimination of all sources of cancer evil -- stem cells, as well as the evildoers they create: the cancer cells," Weiss said.

"It's not as if the stem cells are the only bad guys, and the cancer cells are harmless and can be ignored," Weiss added. "Both populations of cells need to be eliminated. Every cancer is made up of stem cells and a wide variety of cancer cells generated from the stem cells."

As the hypothesis continues to evolve, scientists may discover how to kill the cancer cells and win the cancer war.

The U.S. National Cancer Institute now wants to step up the pace on cancer stem-cell research. Check out current clinical trials here: http://www.cancer.gov/clinicaltrials