MD

News

Friday, November 28, 2014

Advertise with us »

What happens when stem cells go awry? 'U' prof. wonders aloud

Max Collins/Daily
The Detroit Renaissance Center where the World Stem Cell Summit took place this week. Buy this photo

BY SUZANNE JACOBS
Daily Staff Reporter
Published October 6, 2010

DETROIT — Embryonic and adult stem cells have captured the imaginations of scientists and researchers looking for the next breakthrough in regenerative medicine. For Max Wicha, director of the University’s Comprehensive Cancer Center, the question of what can happen when stem cells go awry is just as important.

Wicha, also a professor of internal medicine at the University’s Medical School, posed this question to a crowd of about 35 people at the beginning of his presentation on the final day of the sixth annual World Stem Cell Summit — an international, three-day gathering of leaders in stem cell research — held this year in Detroit.

Just as the majority of stem cell research focuses on the study of adult and embryonic stem cells to regenerate damaged or diseased tissue, so did the numerous discussions and presentations at the summit. Wicha’s presentation on cancer stem cells — cells within a tumor that fuel the tumor’s growth — stuck out on the summit agenda.

In 2003, University researchers reported the first discovery of cancer stem cells, or CSCs, in breast cancer tissue. These cells have since been discovered in many other types of cancer, including those that affect the brain, head, neck, colon and pancreas.

CSCs constitute only about 1 to 5 percent of all cells in a malignant tumor, but despite their relatively small proportion, these cells are responsible for regenerating new cancer cells.

That’s the reason, Wicha said, he and other scientists believe an effective cancer treatment must specifically target CSCs.

Wicha acknowledged that in recent years, existing treatments that don’t target CSCs have still lowered the death rates of certain types of cancer. As a breast cancer specialist, he pointed out that the death rate from breast cancer saw a “precipitous fall” after 1990, and breast cancer patients are now 25 percent less likely to die from the disease than they were 20 years ago.

But the success of current cancer treatments, Wicha said, is largely due to early detection and prevention. He said doctors still struggle to treat advanced cancers and that certain diagnoses like that of pancreatic cancer still coincide with high death rates.

Wicha added that the advances in treatment have thus far been incremental and not dramatic, because scientists have been targeting the wrong cells.

According to Wicha, cancers are “driven” by cells that can make exact copies of themselves through a process called self-renewal — a distinct characteristic of stem cells. When the self-renewal process in these cells becomes deregulated, cancer develops.

The CSCs that are responsible for cancer development are resistant to treatments like chemotherapy that shrink tumors, so after the treatment, the CSCs constitute a higher percentage of the total cells in the tumor, Wicha said.

Wicha said that in general, shrinking tumors does not necessarily increase a patient’s lifespan because it does not attack the root of the disease.

“Tumor shrinkage does not correlate well with patient survival,” he said.

A treatment that will effectively cure a patient, Wicha said, is one that will stop metastasis — the spread of the disease to other parts of the body. About 99 percent of deaths from breast cancer are due to metastasis, he added.

Scientists have determined that CSCs and not other cancer cells are responsible for metastasis.

In collaboration with researchers at Baylor College and the Dana Farber Cancer Institute, the University has completed one clinical trial in testing a CSC-targeting drug. Anne Schott, an associate professor in the University's Medical School’s Department of Internal Medicine, was the principal investigator for the trial.

The study involved 35 participants with metastatic breast cancer. According to Wicha, all of the participants tolerated the treatment well. Nine of them, he said, underwent biopsies both before and after treatment, and they all showed a decrease in the percentage of CSCs, which is exactly the opposite of what happens with chemotherapy.

Wicha said the question remains whether patients will ultimately benefit from the treatment. He estimated that after phase two studies of the drug, which will begin in one to two years and last for about two years, scientists will be able to determine whether this treatment is beneficial. In total, the process should take roughly five years.

One problem with this kind of research, Wicha said, is that a documented increase in survival rate is often the proof necessary to declare a drug successful, but that kind of proof could take years to acquire.


|