Stem Cell Therapy Effective in Targeting Metastatic Cancer

Public Library of Science, December 24, 2006

Since they would be unable to bear the doses of treatment they would need to eliminate the tumors, patients with advanced cancer that has spread to many different sites often do not have many treatment options.

A technique to treat cancers that have spread throughout the body more effectively may have been discovered be researchers at City of Hope and St. Jude Children's Research Hospital. So that normal tissue neighboring the tumor and throughout the body remain relatively unharmed, they used modified neural stem cells to activate and concentrate chemotherapeutic drugs predominately at tumor sites.

"This approach could significantly improve future treatment options for patients with metastatic cancer," said Dr. Karen, M.D., assistant professor of Hematology/Hematopoietic Cell Transplantation and Neurosciences at City of Hope. "It not only has the potential to destroy residual tumor cells, but it should also improve patients' quality of life by minimizing toxic side effects such as nausea, diarrhea or bone marrow suppression."

The study will be published Dec. 20th in PLoS ONE. A second paper with comprehensive results from the study has been accepted for publication in the January issue of Cancer Research.

Toxic to naturally fast-growing cells in the body such as intestinal cells and hair follicles, most chemotherapy drugs affect both normal and cancerous tissue. However, Dr. Karen and her colleagues have developed a way to localize the drug’s effects on tumor cells by developing a two part system to first infiltrate metastatic tumor sites, and then activate a chemotherapeutic drug.

A propensity for invasive tumors to attract neural stem cells is taken advantage of with this technique.

Immunosuppressed mice had been given neuroblastoma cells which formed tumors. These mice were injected with modified neural/progenitor cells. The researchers administered a precursor-drug after waiting a few days to allow the stem cells to migrate to the tumors. After the drug reached the stem cells, the drug interacted with an enzyme the stem cells expressed, and was converted into an active drug that kills surrounding tumor cells. After the first phase of precursor-drugs was administered for two weeks, there was a subsequent two week break. A second round of drugs and stem/progenitor cells were administered following the break.

At six months, one hundred percent of the neuroblastoma mice were healthy and tumor free. All the neuroblastoma mice died within a two-and-a-half month period without treatment.

Neuroblastoma represents 6 to 10 percent of all childhood cancers worldwide, with higher proportions in children under 2 years of age. The results of the study hold promise for treating neuroblastoma as well as treating other solid tumors that metastasize.

"The results are especially important in the case of high-risk neuroblastoma, because treatment-resistant cancer returns in as many as 80 percent of children, and the majority die of their disease," said co-principal investigator Danks.

The effectiveness of this procedure in primary and metastatic tumors in the brain had previously been published by Karen and her colleagues. This is the first research to demonstrate that it is also effective in a metastatic cancer model, targeting multiple solid tumor sites spread throughout the body. Future preclinical trials are being planned for other tumors as well as they speculate that the technique could also be applied to other malignant tumors including, prostate, brain, colon, and breast cancer.