At St. Jude, Breakthrough Science Is Lighting the Way for Brain Tumor Treatment

Recent decades have included remarkable progress in understanding and treating childhood brain tumors. Molecular studies of childhood brain cancer have been practice-changing for people like Giles Robinson, MD, Director of the Division of Neuro-Oncology and Co-Leader of the Cancer Center Neurobiology and Brain Tumor Program (NBTP) at St. Jude. 

Understanding the molecular composition of brain tumors and the traits of different subtypes of tumors have allowed clinicians to improve survival and reduce side effects for what were once considered incurable cancer subtypes. Incremental advances in pediatric brain cancer are driving progress toward safer, more effective cures.

When Robinson first started at St. Jude in 2007, all high-grade gliomas (HGG) — a broad term used to describe aggressive tumors that form in the brain and spine from glial cells — were treated with radiotherapy. The clinical trials that were available tried one drug after another without knowing what to target. Tumor tissue was rarely sampled because it was thought to be too difficult and dangerous to operate, leading clinicians to resort to “treating tumors in the dark,” Robinson said. 

Brain tumors represent the most common solid tumor of childhood, and HGGs make up the largest fraction of this group of tumors. But survival outcomes can vary greatly, based on the different genetic subgroup of tumor as well as the location, age of onset and gender predilection.  

While survival of patients with high-grade gliomas remains low overall, Robinson said he and his colleagues, like Suzanne Baker, PhD, in the NBTP, are developing a greater understanding of the diseases and how best to control tumor growth and lengthen lives of the children who have them. 

In this era of advanced genome sequencing, the brain tumor program is studying tumor tissue samples from patients to learn what genetic mutations drive high-grade gliomas and, therefore, develop more effective drugs and clinical trials to target the disease. If treatment of these tumors used to be like working in the dark, the molecular analysis done today is like shining a light on the tumor.

“Incredibly, for a few patients with HGG, this knowledge has resulted in targeted therapy, where some patients are cured or have had their life significantly lengthened by drugs that target the mutation found in their tumor,” Robinson said.

In some rare cases, patients at St. Jude have had HGG with one of the mutations commonly found in adult lung cancer. Using targeted drugs designed for those mutations led to a few encouraging results.   

“However, for most children with HGG there is no known cure, but there is hope that we can find one,” Robinson said. “We now know what driver mutations are present in these tumors and that if we can figure out ways to inhibit these mutations, we can stop the cancer cells from growing.”

Within pediatric neuro-oncology, doctors and researchers face the added challenge that if brain cancers relapse after conventional treatment, they behave more aggressively and have poor prognoses. For example, in the 30% of medulloblastoma cases that relapse after therapy, only 10% of the patients survive. 

Not long ago, most patients died of relapsed tumors within one to two years of a tumor’s return. But scientific understanding is leading to newer treatments for children at St. Jude with relapsed brain tumors, allowing double to triple that time.

Most importantly, through working with Paul Northcott, PhD, we are now developing a new technique called liquid biopsy, Robinson said. Earlier interventions may lead to better results for some tumors.  

Despite the difficulty in treating children who are facing heart-wrenching odds with relapsed or difficult to treat brain tumors, Robinson finds hope in the research being pursued at St. Jude. “Huge changes are happening in the world of pediatric brain tumors because of this research, and when we successfully show that a new therapy works, our research raises the bar of conventional care.”