ASCO 2020 Pediatric Oncology Award Goes to Dr. Alice Yu, a Pioneer of a New Approach to Neuroblastoma Treatment

With a medical career spanning more than 40, Dr. Alice Yu heads the Department of Pediatrics at Rady Children's Hospital in San Diego, United States. Through her work here, the first successful approach targeting a non-protein antigen, immunotherapy, was pioneered by Dr. Yu, who also guides neuroblastoma research as part of the Children's Oncology Group (COG) neuroblastoma steering committee.

Alice Yu (MD, PhD), a physician at the University of California San Diego School of Medicine, received the ASCO 2020 Pediatric Oncology Award for her contributions to Pediatric Oncology. This award was first presented in 2002 to Dr. Alfred G. Knudson (MD, PhD), who had demonstrated outstanding leadership/achievement in pediatric oncology. Dr. Yu states that, early in her career as a medical student, she had not considered pursuing pediatric oncology. Let us look at her interview with the American Society of Clinical Oncology (ASCO-Daily News).

Note: Neuroblastoma is a type of cancer originating in the nervous system, which carries messages from the brain throughout the body. It usually begins in nerve cells in the adrenal glands. The adrenal glands secrete important hormones that regulate heartbeat, blood pressure and blood sugar. Neuroblastoma often occurs in early childhood.

"At that time, the vast majority of children with neuroblastoma were dying, and I thought I would not enjoy working in this field. However, during my residency, the improved survival of many children with leukemia gave me hope that the same success could be achieved in pediatric oncology." Dr. Yu says that longer survival and the development of treatments for neuroblastoma and other childhood cancers have made her happy with her career choice. She added, "It is an exciting field. Although I was not drawn to it early in my professional life, I am very pleased with my choice". So, what was the study that marked an important turning point in Dr. Yu's career?

A New Cancer Drug Born of Determination and Perseverance

Gangliosides, composed of glycosphingolipids and located on the outer surface of the cell membrane, play important roles in cell-to-cell communication, growth and differentiation. GD2, a disialoganglioside belonging to the ganglioside group, is displayed on the surface of many different tumors, including neuroblastomas. Recognizing it as a good biomarker, Dr. Yu developed what is now known as dinutuximab, the anti-GD2 antibody (code name ch14.18). By binding to GD2 displayed on the surface of cancer cells, the antibody triggers the recruitment of immune cells to the area, enabling tumor cells to be destroyed. Clinical trials showed increased survival in patients with high-risk neuroblastoma, and it was approved in 2015 by the United States Food and Drug Administration (FDA). Designed to bind to GD2, the monoclonal antibody dinutuximab is administered with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 and 13-cis-retinoic acid in pediatric patients with high-risk neuroblastoma.

Although the positive results of clinical studies led the antibody trials into phase II clinical trials, the researchers unfortunately had difficulty finding a pharmaceutical company to support them. Because neuroblastoma was the most common cancer in childhood, pharmaceutical companies did not want to take the risk and refused to invest. Following these setbacks, Dr. Yu decided to fly to Washington with a bag containing patients' X-rays and pathology results. As a result of her determination, the National Cancer Institute decided to support the phase III stage of the research.

In the study conducted with more than 200 patients, a significant increase in survival and overall survival was observed in patients who experienced no complications after treatment. The drug's safety was also demonstrated in other studies; its toxic/harmful effects were identified but were stated to be manageable. Following the positive results with the drug tested, Dr. Yu said, "The immunotherapy we tested has become the new standard treatment for patients with high-risk neuroblastoma", assessing the outcome achieved after prolonged efforts. Potential new biomarkers were also identified during the studies. Dr. Yu stated that their new goal was to increase the effectiveness of immunotherapy by reducing its toxic effects as much as possible.

The approval of dinutuximab marked the first new immunotherapy targeting a glycolipid molecule, thereby expanding the range of potential targeted drugs. The research conducted by Dr. Yu and her team and the innovations they pioneered have paved the way for studies of other glycolipids, such as Globo-H ceramide, that could be used as treatment targets in adult cancers, such as breast cancer, beyond childhood cancers.

• All ASCO 2020 Awards