After analyzing hundreds of proteins produced by the DNA of tumor cells, researchers have identified one protein that may be central to a new treatment for the often-fatal childhood cancer neuroblastoma. Oncologists hope to translate the finding into pediatric clinical trials of a drug that blocks the protein's activity.
"Our study implicates this protein as a promising treatment target for high-risk neuroblastoma," said pediatric oncologist Kristina A. Cole, M.D., Ph.D., of the Cancer Center at The Children's Hospital of Philadelphia. "The fact that drugs acting on this protein are already being studied in clinical trials for adult cancers may hasten the process of testing this treatment strategy in children."
Cole is the lead author of a study published online Feb. 2 in the Proceedings of the National Academy of Sciences.
Neuroblastoma, a cancer of the peripheral nervous system, usually appears as a solid tumor in the chest or abdomen. It accounts for 7 percent of all childhood cancers, but because it is often aggressive, it causes 15 percent of all childhood cancer deaths. While low-risk forms of neuroblastoma may spontaneously disappear, in high-risk forms, the cancer tends to return after initial treatment, usually with lethal results.
In the current study, the Children's Hospital researchers performed a comprehensive screen of hundreds of protein kinases encoded by the DNA of neuroblastoma cells. As enzymes, kinases stimulate chemical reactions in the cell, and have been implicated in many cancers as promoting growth and survival of cancer cells. The study team used RNA interference, a powerful research tool that uses small RNA sequences to prevent cells from producing proteins, to interrupt the action of each of the more than 500 kinases made by neuroblastoma tumor cells.
Methodically testing each kinase, one after the other, the researchers identified 30 kinases that, when depleted, caused neuroblasto
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Children's Hospital of Philadelphia