A new hope for cancer treatment

BY ARIKIA MILLIKAN

Published February 2, 2007

While some stem cells are known for their potential to cure cancer, University researchers have discovered evidence that a different kind of stem cell causes cancer.

Understanding them may revolutionize the way cancer is treated.

Now researchers at the University's Comprehensive Cancer Center say they have found exactly which cells are responsible for pancreatic cancer, which kills the fourth-most people of any type of cancer.

The cells of a tumor are like weeds in a garden. Pulling the weeds will make them go away for a while, but unless the root of the weed is destroyed, they will keep growing back.

Cancer stem cells may make up less than 1 percent of a tumor, but research suggests they drive the growth of the entire tumor.

Like other types of stem cells - such as adult and embryonic - cancer stem cells have the abilities to make exact copies of themselves and differentiate to make many other kinds of cells. They also live much longer than ordinary cells.

However, unlike adult and embryonic stem cells, which are crucial to development and the production of healthy cells, cancer stem cells make the wrong amount or the wrong type of cell, resulting in tumors that impair vital functions.

"We know out of thousands or millions of cells in a tumor, there are only a small percent that cause problems," said Mark Prince, residency director of the University's Department of Otolaryngology, where he researches the stem cells responsible for head and neck cancers.

One theory suggests that cancer stem cells are either a mutant version of adult stem cells that replenish all of one's healthy bodily tissue or are produced by those cells.

Although the hypothesis has existed for decades, a team of University researchers discovered the actual cancer stem cells in 2001.

They found the first stem cell in a solid tumor while studying breast cancer. Over the past six years, University researchers have gathered evidence that points to cancer stem cells as the culprit behind several types of cancer, if not all.

So far, cells fitting the bill have been found in breast, head and neck, leukemia, brain, prostate, blood, colon and melanoma tumors, said Mix Wicha, director of the Comprehensive Cancer Center.

"I believe that every cancer has got a stem cell," he said.

Results from a study headed by Diane Simeone, director of the Gastrointestinal Oncology Program at the Comprehensive Cancer Center, were released in the Feb. 1 issue of Cancer Research magazine. The study identified markers associated with the stem cells in pancreatic cancer.

This research will provide a starting point for the development of treatments for pan creatic cancer, Simeone said.

Simeone and other researchers were able to identify cancer stem cells by taking human pancreatic tumors, separating the individual cells and categorizing them by proteins on the cell surface. They then injected different combinations of tumor cells into mice without immune systems.

In Simeone's experiment, she found that the mice that readily grew tumors had been injected with cells marked by three types of surface proteins, identified as CD44, CD24 and ESA. This small group of cells, which makes up less than 1 percent of pancreatic tumor cells, was able to produce a tumor closely resembling the original. The other cells in the original tumor did not grow tumors in mice.

CD44 is one of the markers Wicha and Prince identified as a cancer stem cell in breast as well as in head and neck tumors. This common denominator provides a starting point for researchers to look for stem cells in other cancers.

But while Simeone reports that CD24 caused tumors in the mice, Wicha said it does not generate breast cancer tumors.

This finding supports the idea that each type of cancer may have its own unique blend of cancer stem cells.

With the knowledge of pancreatic stem cell markers as well as those for other types of cancer, researchers can approach treating cancer in a totally different way.

According to Wicha, Simeone and Prince, who often collaborate on projects, many modern cancer treatments like radiation and chemotherapy fail because they are not targeted at the cancer stem cells.

Currently, treatment success is measured by how much a tumor's mass shrinks. The problem with this logic, the researchers said, is that cancer stem cells are resistant to current standard therapies. While 99 percent of the tumor cells may be destroyed, if that nagging 1 percent remains, the whole tumor has the potential to grow back.

In the short term, Prince, Wicha and Simeone said they would work to improve their abilities to locate and study the key cells and find out what makes them unique.

Eventally this understanding will allow researchers to develop new treatments, the researchers said.

Wicha said he is optimistic but that it will be a challenge to find a way to destroy the cancer stem cells without damaging other healthy cells.

"If we could be more specific about killing cancer stem cells, it seems quite logical that treatment would be more effective," Prince said.