Among the genes found to be switched on by retinoids was BMP-2 (bone morphogenetic protein-2), which codes for a protein thought to play a role in cell death and in the development of nervous system tissue that gives rise to medulloblastomas.
The addition of purified BMP-2 protein to medulloblastoma cells caused significant cell death, even to cells that were resistant to retinoids. Further, when retinoid-senstive cells were grown in close proximity to resistant cells, both types of cells were killed after addition of retinoids. This result indicates that BMP-2 protein secreted by the sensitive cells triggers killing of the neighboring drug-resistant cells.
"This has significant clinical implications," Hallahan said. "Tumors contain mixture of cell types, some of which may be resistant to certain drugs. Our results suggest that retinoid treatment could still manage to kill resistant cells that are in proximity to drug-responsive cells in the tumor."
Olson said that it also suggests that BMP-2 or other proteins "downstream" in the retinoid-induced cell-death cascade could be potential targets for new anticancer drugs.
A proposed clinical trial for high-risk pediatric medulloblastoma patients to compare standard therapy plus retinoids to standard therapy alone is now under review by the Children's Oncology Group, a National Cancer Institute-supported clinical trials cooperative group whose member institutions are devoted exclusively to childhood and adolescent cancer research. Olson, who will serve as principal investigator of the study, hopes to begin the
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Contact: Susan Edmonds
sedmonds@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
4-Aug-2003