On Target
New Approaches to Targeting and Killing Neuroblastoma Cells
Sandra Nelson, PhD, at the Genome Research Institute, is collaborating with investigators in the Cincinnati Children's cancer program to screen a library of 250,000 compounds to identify candidates for new anticancer drugs. |
| 1981 Cincinnati Children's opens one of the first pediatric bone marrow transplant units in the country and becomes one of the first to perform BMT for neuroblastoma. |
| 2007 The Cincinnati Children's cancer program and the University of Cincinnati Genome Research Institute collaborate to develop new drugs for neuroblastoma. |
It is one of the biggest advances in medicine of the last 50 years.
Fifty years ago, childhood cancer was almost universally fatal. By the mid-1970s, the overall survival rate was nearing 60 percent. Today, it's nearly 80 percent, and for some cancers, the rate is even better – up to 95 percent survival for children with the most common forms of leukemia.
It's an amazing achievement. But for some types of childhood cancers, obstacles to progress remain.
Neuroblastoma is one of those.
Neuroblastoma is a solid tumor cancer that begins in the sympathetic nervous system. It most often strikes children under age 5.
For children under age 2 and those with a single mass of tumor, the combination of surgery and chemotherapy has led to cure rates of 90 to 95 percent. The cancer program at Cincinnati Children's Hospital Medical Center is a referral center for these patients, offering expertise in surgery, anesthesia and chemotherapy techniques for infants with cancer.
But in older children and those with metastatic disease, neuroblastoma is a much tougher enemy. The tumor cells are often able to survive ordinary doses of chemotherapy and radiation, leading to relapses that are difficult to cure.
Over the past three decades, Cincinnati Children's has been a leader in developing high-dose chemotherapy with bone marrow transplant techniques and drug protocols that have improved outcomes for high-risk neuroblastoma. Today, these transplants are an important part of the standard of care.
Beating the Odds
Jacob Hartig, 13, is one child who beat high-risk neuroblastoma. Jacob was 2 when he was diagnosed. He had surgery, followed by intensive chemotherapy and radiation, and then a bone marrow transplant. But after nearly a year of treatment, the cancer was still there.
"Jacob was 3, and his doctor told us he wouldn't make it to his fourth birthday," his mother, Lisa, says, fighting back tears.
Few treatment options were available. Jacob had had so much chemotherapy, he couldn't receive more. As a last resort, his parents were offered an experimental treatment with cis-retinoic acid, a type of vitamin A that affects cell growth. It is commonly used to treat acne, but early clinical trials suggested that high doses could slow the growth of cancer cells.
When Jacob took it, the drug was only available in gel caps. Since he couldn't swallow the pill, his parents squeezed the thick gel onto a spoon, and he licked it, for almost two years. It saved his life.
Today Jacob is an active teen who dreams of playing basketball for the University of Kentucky, and cis-retinoic acid has become part of the standard of care for high-risk neuroblastoma.
High-dose chemotherapy with marrow transplant and drugs such as cis-retinoic acid have improved the outcome for children. In 1980, cure rates for high-risk neuroblastoma were less than 10 percent. Today, they have reached 35 to 40 percent. However, enormous challenges remain for curing the majority of patients.
Seeking New Approaches
"We urgently need new treatments that target and kill neuroblastoma cells, and Cincinnati Children's is continuing to be a leader in advancing care," says John Perentesis, MD, director of the Oncology Program. Dr. Perentesis and his colleagues at Cincinnati Children's and the Genome Research Institute of the University of Cincinnati have begun searching for new drugs that target growth mechanisms unique to neuroblastoma cells. They are screening a library of 250,000 compounds, seeking promising candidates for anticancer drugs. "This drug library is an extraordinary and unique resource," says Dr. Perentesis.
Another team, led by Timothy Cripe, MD, is genetically engineering viruses that target and kill neuroblastoma cells. With promising results in the laboratory, the team is planning to develop the technology for use in patients.
Innovative work is under way in the clinic, as well as the lab. In efforts led by Brian Weiss, MD, Cincinnati Children's is one of just four cancer centers testing MIBG, a radioactive molecule that targets and kills neuroblastoma cells, without damaging normal cells. Very few centers have the infrastructure to conduct this intensive, technically demanding trial.
"MIBG is one of the most promising treatments on the horizon, and our innovative laboratory research offers hope for discovering new anticancer drugs," Dr. Perentesis says. "We're excited about contributing new knowledge that may help change the face of neuroblastoma treatment in the future."
