1996 Archives

MORE HOPE IN THE FIGHT AGAINST NEUROBLASTOMA

The next 10 years could bring tremendous hope in the fight against neuroblastoma at St. Jude Children's Research Hospital. The pharmacology department continues to investigate new drugs to combat the disease. Gene therapy researchers continue to improve a tumor vaccine. Basic research departments will work in the future to unlock the mysteries of why neuroblastoma cells develop in the first place.

"We're at a very important threshhold in the research of neuroblastoma at St. Jude and I am very optimistic," said Victor Santana, M.D., a St. Jude physician who treats neuroblastoma. "A strong team approach between the clinicians and the basic scientists is important in finding new clues to cure this disease."

Victor Santana, M.D., with Camden (right) and Raymond (left) who are neuroblastoma patients.

Neuroblastoma is the most common solid tumor found generally in children younger than 5. Between 15 and 20 patients are diagnosed with neuroblastoma each year at St. Jude Hospital. About 500children are diagnosed nationwide. Neuroblastoma is a cancer of the sympathetic nervous system, which is part of the nervous system that influences the activity of voluntary muscles, cardiac muscles and glands. It is believed the disease arises during development of the fetus. It involves a group of cells known as neuroblasts (primitive neural cells). These embryonic cells eventually will develop into nerve cells or neurons.For unknown reasons, some of these cells become malignant. Neuroblastoma tumors can actually appear anywhere along the sympathetic nervous system, which runs from the base of the skull to the tailbone. Tumors are most commonly found near the adrenal gland or in the chest.

The most common form of treatment is surgery if the disease is localized. However, the disease usually spreads to other parts of the body in the majority of cases. If it has spread, chemotherapy is the most prevalent treatment. Radiation is sometimes used. Bone marrow transplant is an option for some patients.

One of the most puzzling mysteries of neuroblastoma is why infants have a much greater chance of surviving the disease than older children. Survival rates overall are at about 50 to 55 percent. But infants and toddlers have a 80 to 90 percent of survival. That compares to older children, who, in later stages of disease have as little as a 20 percent chance of survival. The median age of diagnosis is about 2 years old. Some 90 percent are diagnosed before age 5.

Doctors hope basic research will solve the age/survival riddle. "Hopefully all this research into neural development and identification of genes that have to do with the development of the brain and nervous system may give us some clues about what went wrong during development. That's something that's very exciting about the future," Santana said.

St. Jude Hospital has played a role in the history of neuroblastoma research and treatment. In 1977, Ann Hayes, M.D., and Alexander Green, M.D., identified a treatment using a combination of two drugs, cytoxan and adriamycin. The therapy proved extremely effective in curing infants. Seven years later in 1984, experimental oncology chairman Tom Look, M.D., and his team devised a way to determine the level of DNA in a neuroblastoma cell compared to a level in a normal cell. This "DNA index" provided a way to predict the prognosis of infants with neuroblastoma. As a result, those with a good prognosis can receive a lighter treatment and still be cured. Those with a poor prognosis receive more powerful treatments in hopes of obliterating the cancer.

One promising area of neuroblastoma research is the development of a tumor vaccine. Twelve St. Jude patients have received this treatment since the early 1990s, said Laura Bowman, M.D., a physician who treats neuroblastoma. Immunotherapy is promising because neuroblastoma is a cancer that has many documented cases of spontaneous remission - where the immune system may play a role. The vaccine is made up of tumor cells engineered to produce Interleukin-2, which is a component of the immune system. The tumor vaccine will hopefully cause the patient's immune system to recognize the tumor as a foreign body. This should spark the immune system to attack and destroy the tumor.

The development of new anti-cancer drugs is another exciting area. A new group of compounds called camptothecins that inhibit a key enzyme in the nucleus of the cell have shown encouraging results in animal models. Two of these drugs, topotecan and CPT-11 can cause regression of neuroblastoma in tumor-bearing animals. Both of these drugs will be available for clinical trials and will be incorporated into a new study to be launched later this year.

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