Advancing Pediatric Cancer Research

Dr. Mark Israel, Director of the Cancer Center

A three-year-old girl complained of pain in the back of her head. Occasionally, she would vomit for no apparent reason. Dismissed as the flu, the symptoms continued on and off for months, and gradually became more frequent. Is it a food allergy? A virus? Something the child will outgrow?

In this case, a computerized tomography (CT) scan uncovered a medulloblastoma, the most common malignant brain tumor in children. Even with surgery, radiation therapy, and chemotherapy, there is only a 50 percent five-year survival rate. This tumor type has a tendency to spread to other areas of the brain and the spinal cord.

The ultimate goal for Mark Israel, MD (Director of Norris Cotton Cancer Center and Professor of Pediatrics and Genetics at Dartmouth Medical School) is to understand the genetic changes in brain cells that make them become cancerous. He was recently awarded two grants from the Theodora B. Betz Foundation totaling more than $2 million in support of his research on brain tumors.

In one study, Israel proposes to develop mouse models that correctly reflect the genetics and biology of medulloblastoma. By recreating the genetic abnormalities found in human medulloblastoma in mice, Dr. Israel believes he can generate animal models that accurately mirror the human form of the disease.

The origin of medulloblastoma remains controversial, but accumulating data suggests that it begins with abnormal growth in the external granular layer of the developing cerebellum. Genetically, these tumors sometimes show a mutation in the APC gene, which causes it to be inactive. APC is a "tumor suppressor gene," a gene that usually blocks the development of cancerous growth. Israel hopes to better define the pathways that cause malignant growth of neural cells, and thus play a key role in the growth of medulloblastomas.

It's important work. The opportunities to develop treatment approaches for childhood brain tumors are limited by the small number of children able to participate in clinical trials. There is also concern about exposing a child's developing nervous system to unknown toxicities. In the future, Israel will use these mouse models for the evaluation and development of new therapeutic approaches.

"The availability of new models may have an important impact on the survival of children with medullo-blastoma," Israel says.