Targeting tough-to-treat pediatric cancers

When Gideon’s parents found bruises on his body and a lump on his head, they took their baby to the pediatrician.

In the clinic, his doctor also felt a mass in Gideon’s abdomen.  Gideon was referred to St. Jude Children’s Research Hospital® where tests determined he had high-risk neuroblastoma, an aggressive and rare type of cancer that almost always affects children.

He started his first dose of therapy at St. Jude three days after his visit to the pediatrician. Scans showed the cancer had spread throughout his body, even causing the lump on his head. But quickly, his treatment began to work. In addition to chemotherapy, Gideon had surgery, a bone marrow transplant and radiation therapy at St. Jude. He also received a novel antibody therapy manufactured on the St. Jude campus. 

After more than a year of treatment, Gideon went home cancer-free in January 2017. Survivors of childhood cancer like Gideon who are treated at St. Jude receive long-term follow-up care. So, until he turns 18, Gideon visits St. Jude once a year for checkups at the After Completion of Therapy (ACT) Clinic.

Back at home, Gideon enjoys school and geology, especially digging for rocks. He also plays baseball and is a loving big brother.

Hopeful stories like Gideon’s fuel the work of clinicians and researchers like Julie R. Park, MD, who is now Chair of the Department of Oncology at St. Jude. She took over the leadership post a little more than a year ago, leaving Seattle where she had spent 30 years working to develop new therapies and improve survival rates for children with cancer. 

Park is also the Associate Director for Translational Research in the Comprehensive Care Center at St. Jude. She works with teams of doctors and researchers who perform translational research – that is, how to turn the cutting edge, innovative work done in the labs of St. Jude into more effective treatments in clinics that treat kids with pediatric cancers. Through these roles, Park is hoping to chart substantial progress in tough-to-treat pediatric cancers like neuroblastoma.

She assumed the role as Chair after the esteemed St. Jude oncologist Ching-Hon Pui, MD. Pui is internationally renowned for his work to improve survival rates and the quality of life for kids with acute lymphoblastic leukemia (ALL). He continues his clinical and research work to improve outcomes in patients with ALL, with a focus on clinical research in the Asia-Pacific region for St. Jude Global.   

Park grew up in Rhode Island and received her early medical training at the University of Vermont in Burlington, Vermont. She thought she’d spend the rest of her life in that tightknit northeast corner of the U.S., but then she traveled across the country to Seattle, Washington, to complete her medical training in pediatrics and pediatric hematology/oncology.

 It’s also the place that first sparked her interest in pediatric cancer research. “I found my true love in what I wanted to do: to treat children with cancer and improve their outcomes,” Park said.

That principle still drives her. Especially when she thinks of cases like Gideon’s.

“Neuroblastoma, I think, is the most fascinating and yet most frustrating cancer we treat in childhood,” Park said.

Children can be diagnosed with neuroblastoma as early as the day they’re born, Park said, but the average age for diagnosis is 2. Neuroblastoma is a difficult disease to detect in early stages and doesn’t follow predictable patterns in how it behaves in children, she said. 

Some children with neuroblastoma can have widespread disease, including nodules under their skin and enlarged livers, but remarkably, the disease resolves on its own. Under the microscope, those neuroblastoma cells look just like any other cancer, and yet they go away on their own, Park said. On the other hand, there are children with widespread disease in their bones and their bone marrow, and in these children, neuroblastoma does not go away on its own. In fact, if left untreated, the children with this form of neuroblastoma will likely die, Park said. 

“And what we don’t understand is what causes the spontaneous regression of neuroblastoma in some children and not others,” Park said.

She points to a curve on a graph that shows survival rates climbing over the last 20 years. But that improvement is not nearly as dramatic as she’d like.

“We are treating these children with the most intensive therapy we have at our disposal and yet in some cases, 50 percent of them will not survive. That’s just not acceptable,” Park said. “And those surviving still have multiple long term health effects because of the intensity of the treatment. We have to do better for them.”

Fortunately, Park is overseeing further research on one of the biggest advancements in neuroblastoma research today: how to harness the power of the immune system to detect and kill neuroblastoma cells. 

“There are antibodies that are proteins that recognize tumor cells and stick to it. They’re like a flag and tell the immune system be a Pac Man and go gobble up that tumor cell,” Park said, adding, “St. Jude has made its own antibody and very exciting trials have shown the addition of the antibodies early on in treatment may improve outcomes.”

It was this earlier clinical trial – concluded before Park assumed her current roles and led by St. Jude oncologist Sara Federico, MD, and now-retired oncologist Wayne Furman, MD – that made it possible for Gideon to receive antibody therapy to treat his high-risk disease. Following the encouraging results of that clinical trial, Park said she’s excited to join the team and help shepherd it through the next phase of trials and study.    

Relying on antibody therapy more could potentially allow doctors to pull back on more toxic therapies like radiation and chemotherapy.

Cancer cells tell your body to bring in normal cells to protect them.

“I like to say it’s like building a moat around the castle,” she said. “The cancer cells signal to all the parts of our immune system to help protect them. Parts of the body that should not be doing this end up guarding  the tumor cells to prevent the normal immune system from doing their job. We have to understand how and what the tumor cells are telling the rest of the body. It’s called a tumor microenvironment. Why does the immune system become so dumb when cancer cells are communicating with it? Why isn’t it attacking?”

Until now, a variety of clinical trials studied these questions in isolation across various cancers. But Park envisions a more comprehensive platform of clinical trials that study and share everything from why some kids are more likely to develop cancer to the molecular underpinnings of tumors, or the immunologic effect of tumors, and better understanding tumor microenvironments so doctors can manipulate their weaknesses to destroy them more effectively. 

It’s the kind of ambitious, far-reaching work only possible at a place like St. Jude, Park said. Thanks to generous donors, researchers have the freedom to study, collaborate and communicate across and outside their individual disciplines and expertise to share information about what they learn about the complex nature of the worst diseases to threaten children’s lives.

“We should learn from each patient so we can continue to develop new treatments and therapies,” Park said.

Her vision for the future: oncology that is built on collaboration and innovation.

“Researchers have to collaborate both internally and externally so that we can get cures faster for kids with cancer.”