Failure to recognize the role of stem cells in metastasis may have led cancer researchers up “blind alleys” in countless clinical trials, said Max S. Wicha, M.D., founding director and distinguished professor of internal medicine at the University of Michigan Comprehensive Cancer Center, speaking at the National Comprehensive Cancer Network’s 12th Annual Conference.
With tumor shrinkage the primary guidepost of any new treatment, valuable therapies may be aborted too early in their experimental life, he said.
At the same time, clinical-trial measurements that focus only on a tumor’s diminishing size may explain why some new therapeutic treatments have failed to work. If the tumor’s stem cells run amok even as the tumor’s girth diminishes, a patients’ life may be at stake.
The answer? Begin monitoring whether chemotherapy and radiation treatments work to arrest cancer’s stem cells and their progenitors. Then find ways to make chemotherapy and radiation treatments more powerfully target the tumor’s stem cells while sparing healthy stem cells the body needs.
“In any organ, the stem cells give rise to all the other cells,” Wicha explained. “This process in the body is normally highly regulated.” He and his colleagues at the University of Michigan School of Medicine speculate that cancer arises because of some disruption during the self-renewal or differentiation process.
In tracking the origins of cancer, the common “stochastic model” holds that any of the body’s cells can mutate and begin growing wildly. In contrast, the “cancer stem-cell model,” with its emphasis on stem cells being the only locus of cancer, reactivates a 100-year-old theory, Wicha said. Flow cytometry and other sophisticated laboratory methods have allowed the hypothesis to be tested. “Within cancer, are stem cells driving the malignancy?” Wicha asked, framing the current evolution of cancer stem-cell research.
Experiments at the University of Michigan Comprehensive Cancer Center first identified human “stem cells” in breast cancer tumors in 2003. Since then scientists have gathered more evidence that stem cells and “daughter cells” in breast tumors create floating spherical colonies that help serve as markers.
“Surgeons have been telling us for years we have to get clean margins around the tumors” to help prolong patient survival, Wicha said. Having created new ways to identify stem-cell expression, researchers can now see evidence of breast-cancer stem cells within the tumor, “right at the margin, trying to invade the healthy breast tissue,” said Wicha, who is internationally known for his research in breast oncology, specifically how breast cancer cells grow and metastasize.
Now Wicha is working with the National Cancer Institute to help find simpler ways of identifying the activity of stem cells within a tumor and testing its relation to whether the patient survives or dies. For doctors to track breast-cancer patients’ stem-cell content in hospitals and clinics around the country, simpler and less expensive ways of measuring the markers must be devised, he said.