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Jan 24 2013

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Study Shows Neuroblastoma Evolves Rapidly, Limiting Treatment Targets

neuroblastoma

A recent genomic study of neuroblastoma reinforces the challenges of treating the most aggressive forms of this disease. Contrary to expectations, the researchers found relatively few recurrent gene mutations — mutations that would suggest new targets for neuroblastoma treatment. Instead, the investigators have refocused on how neuroblastoma tumors evolve in response to medicine and other factors.

As part of the National Cancer Institute’s TARGET (Therapeutically Applicable Research to Generate Effective Treatments) initiative, John M. Maris, MD, director of CHOP’s Center for Childhood Cancer Research, led a multicenter research project on neuroblastoma. The largest genomic study of a childhood cancer to date, the TARGET project analyzed DNA from 240 children with high-risk neuroblastoma, with the goal of mapping out a limited number of treatment strategies.

Comprising only 7 percent of childhood cancers, neuroblastoma is nonetheless responsible for 10 to 15 percent of all childhood cancer-related deaths. Affecting the nerve tissue, neuroblastoma usually appears as a solid tumor in a child’s chest or abdomen, and can spread to the lymph nodes, liver, and bones. The average age of neuroblastoma patients is approximately 18 months.

Though great strides have been made in the fight against neuroblastoma (many of them at Children’s Hospital), children with high-risk forms of this disease can face a daunting course of therapy, including surgery, chemotherapy, and radiation. Neuroblastoma is also notoriously complex, with a broad number of gene changes that can give rise to the disease.

The TARGET study’s approach would have represented a significant step forward in the personalization of neuroblastoma therapy. However, the researchers found that there were relatively few recurrent mutations in somatic (non-germline) cells. In the absence of frequently altered oncogenes that drive high-risk neuroblastomas, the investigators concluded that some cases may result from other changes, such as modifications during tumor evolution.

“This research underscores the fact that tumor cells often change rapidly over time, so more effective treatments for this aggressive cancer will need to account for the dynamic nature of neuroblastoma,” said Dr. Maris.

Future treatment strategies could involve devising interventions to deal with dynamic tumor cells that evolve during nervous system development, Dr. Maris noted.

“Personalized medicine is more complex than we had hoped,” said Dr. Maris, who added “this study implies that we must think very differently about how we’ll use genomics to define treatment.”

To read more about the TARGET study, see the full press release. To learn more about the work being done to treat neuroblastoma and other childhood cancers, visit the Center for Childhood Cancer Research website.

Permanent link to this article: http://www.research.chop.edu/blog/study-shows-neuroblastoma-evolves-rapidly-limiting-treatment-targets/

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