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Neuroblastoma expert reviews progress and challenges in fighting difficult pediatric cancer

Children's Hospital of Philadelphia

Sunday, 24 June 2007

Childhood cancers are fortunately rare, but among them, neuroblastoma is a special case, accounting for 7 percent of all childhood cancers, but 15 percent of childhood cancer deaths. It typically occurs as a solid tumor in the abdomen, but also in the neck, chest, and pelvis, developing in the network of the body's sympathetic nervous system. Neuroblastoma is what physicians call a heterogeneous disease; its name includes subtypes of disease that behave very differently. Some cases strike in infants, but spontaneously disappear with minimal treatment, while other cases in older children may be relentlessly aggressive from the start. So precisely defining a given patient's risk level can help oncologists design the best treatment, avoiding the twin pitfalls of undertreating or overtreating any given child.

Better treatments may be on the horizon, but better understanding of neuroblastoma’s precise biology can guide physicians to the best choices among possible options.

John Maris, M.D., of The Children’s Hospital of Philadelphia, describes the current status of neuroblastoma treatment and trends for the near future, in the June 23 issue of the British journal Lancet. Maris is among the world leaders in neuroblastoma research, with a lab holding tissue samples from 5,000 patients--the world's largest sample collection for the disease.

In his paper, Maris reviews new approaches to treatments for a particularly challenging set of patients--children whose neuroblastoma has relapsed in an aggressive form. One particular technique being used and studied at Children's Hospital employs radioactive isotopes that zero in on neuroblastoma cells to selectively kill those cells with radiation. Other tools include retinoids--biological molecules that hone in on cancer cells, angiogenesis inhibitors that cut off a tumor's blood supply, and tyrosine kinase inhibitors that interrupt a critical step in the tumor’s growth process.

“These approaches are targeted therapies--aimed in highly selective ways at cancer cells, but sparing healthy cells,” said Maris. “But in order to best

guide us to the most appropriate treatments, we need greater understanding of the abnormal biological events that give rise to neuroblastoma.” One crucial technique for identifying biological pathways is through studies of the gene mutations and variations involved in different types of neuroblastoma, and Maris’s team is calling on the sophisticated gene-hunting facilities at the new Center for Applied Genomics at Children's Hospital to advance that knowledge.

“Our goal is to match the most appropriate treatment with precise molecular targets in biological pathways, so we can intervene to stop neuroblastoma in its tracks,” said Maris.

Support for the paper was provided in part by the National Institutes of Health, the Children’s Oncology Group, and a variety of private foundations and organizations. In addition to his position at Children’s Hospital, Maris is on the faculty of the University of Pennsylvania School of Medicine. Maris’s co-authors were Michael D. Hogarty, M.D., of The Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine; Rochelle Bagatell, M.D., of the University of Arizona Health Sciences Center and Steele Children’s Research Center of Tucson, Ariz.; and Susan L. Cohn, M.D., of Comer Children’s Hospital and the University of Chicago.

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

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