Targeting Cancer's Own Stem Cells to Fight Recurrence
In the lab, scientists used a virus to thwart tumor's comeback
WEDNESDAY, Jan. 21, 2009 (HealthDay News) -- Scientists have located a group of cancer stem cells or "tumor-initiating cells" which, when targeted with a reprogrammed herpes virus, are prevented from turning malignant.
The finding bolsters the theory that cancer harbors its own secret cache of stem cells that are resistant to conventional therapies and responsible for tumor re-emergence.
Eliminating these malingerers could be key in the fight against certain cancers, such as neuroblastoma, which was the focus of this study.
"This research and this line of research in general is very exciting," added Dr. L. Gerard Toussaint III, an assistant professor of neuroscience and experimental therapeutics at Texas A&M Health Science Center College of Medicine and a neurosurgeon with the Texas Brain and Spine Institute in Bryan. "Their approach is to genetically engineer a virus that would only be turned on in the stem cell population."
This type of virus-against-cancer therapy may be the next generation of anti-cancer treatments, he said.
The study was published online Jan. 21 in the journal PLoS (Public Library of Science) One.
Neuroblastomas, which develop in the nerve tissue of the adrenal gland, neck, chest or spinal cord, account for 8 percent to 10 percent of childhood cancers, the report stated. Remission is common, but so is relapse, and long-term survival in high-risk cases is less than 50 percent.
"The cancer often responds to chemotherapy and more often than not will shrink but too often it comes back," explained Dr. Jeffrey Toretsky, an associate professor of oncology and pediatrics at Georgetown's Lombardi Comprehensive Cancer Center in Washington, D.C. "The promise is that they will be able to successfully create some agent, a virus, that would be able to get at the cells responsible for regrowth."
Experts have theorized that stubborn and apparently undetectable stem cells are left unscathed by existing treatments, linger in the body and eventually reform the tumor or cause the cancer to spread.
"They go into remission then we don't detect the disease at all for one, two, three years, and then it comes back," explained study senior author Dr. Timothy Cripe, professor of pediatrics at Cincinnati Children's Hospital Medical Center and the University of Cincinnati. "Stem cells would explain that. We need to understand those cells and target them."
"If cancers are being seeded by a few cells, they need to be the target. We have maxed-out therapy for cancers, in particular neuroblastoma. We need to identify something novel and different," he continued.
These researchers identified and then grew several lines of human neuroblastoma cells that seemed to have characteristics of neural stem cells -- meaning, among other things, that they could grow into different types of cells including tumors. The cells also carried the protein nestin, which is a marker for nerve stem cells and is also present in neuroblastoma cells.
When the stem cells were infected with a herpes simplex virus which specifically targets nestin, they did not form tumors over the next 60-day period. When infected with a different virus that does not target nestin, mice developed tumors within 40 days. Mice who were uninfected with either virus developed tumors within 30 days.
But, Cripe cautioned, "we used cell lines propagated in plastic dishes. [We need to know] how does that relate to cells in humans?"
There's more on neuroblastomas at the U.S. National Cancer Institute.