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Researchers Find Stem-cell Therapy Effective in Targeting Metastatic Cancer

Patients with advanced cancer that has spread to many different sites often do not have many treatment options,// since they would be unable to tolerate the doses of treatment they would need to kill the tumors.

Researchers at City of Hope and St. Jude Children's Research Hospital may have found a way to treat cancers that have spread throughout the body more effectively. They used modified neural stem cells to activate and concentrate chemotherapeutic drugs predominately at tumor sites, so that normal tissue surrounding the tumor and throughout the body remain relatively unharmed.

"This approach could significantly improve future treatment options for patients with metastatic cancer," said Karen Aboody, 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."

Aboody is the lead investigator of the study done in collaboration with senior investigator Mary Danks, Ph.D., associate member of Molecular Pharmacology at St. Jude Children's Research Hospital in Memphis, Tenn. The study will be published Dec. 20 in PLoS ONE. A second paper with extended results from the study has been accepted for publication in Cancer Research in January.

Most chemotherapy drugs affect both normal and cancerous tissue, which is why they also are toxic to naturally fast-growing cells in the body such as hair follicles and intestinal cells. Aboody and her colleagues have developed a two-part system to infiltrate metastatic tumor sites, and then activate a chemotherapeutic drug, thereby localizing the drug's effects to the tumor cells.

The technique takes advantage of the tendency for invasive tumors to attract neural stem cells. The researchers injected modified neural stem/pro genitor cells into immunosuppressed mice that had been given neuroblastoma cells, which then formed tumors. After waiting a few days to allow the stem cells to migrate to the tumors, researchers administered a precursor-drug. When it 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. The precursor-drugs were administered for two weeks, then after a two-week break, a second round of stem/progenitor cells and drugs were administered.

One hundred percent of the neuroblastoma mice appeared healthy and tumor-free at six months. Without treatment, all the neuroblastoma mice died within two-and-a-half months.

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

"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.

Aboody and her colleagues had previously published the efficacy of this technique in primary and metastatic tumors in the brain. 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. They speculate that the technique could also be applied to other malignant solid tumors, including colon, brain, prostate and breast cancer, and are planning future preclinical trials using those tumors as well.


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