Yael Mossé, MD

Dr. Yael Mossé is a physician-scientist at Children’s Hospital Philadelphia who has spent over two decades advancing research and treatment for neuroblastoma.

She led the discovery of ALK mutations as key drivers of the disease and has translated this work into targeted therapies, including FDA-approved ALK inhibitors. Her lab continues to develop novel approaches—including immunotherapy and protein degradation strategies—to overcome resistance and target additional drivers like MYCN, ATRX, and RAS, with the ultimate goal of improving outcomes for children with high-risk cancers.

Who is Yael Mossé, MD? Dr. Yael Mossé is an attending physician at the Children’s Hospital of Philadelphia and a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, where she also hods the Patricia Brophy Endowed Chair in Neuroblastoma Research. As a physician-scientist, Dr Mossé has dedicated her career to advancing the treatment for neuroblastoma – both by improving outcomes for patients and by using the disease as a model to better understand how cancers develop. She is the recipient of the 2025 CureSearch Acceleration Initiative Award for her project, “Translation of an ALK-directed Antibody Drug Conjugate for Neuroblastoma.”

What is neuroblastoma? Neuroblastoma is a type of cancer that develops in very early forms of nerve cells. It primarily affects infants and young children, with the average age at diagnosis being just 18 months. It is the most common solid tumor in children outside of the brain, with about 700 new cases diagnosed in the US each year.

Why are new treatments needed? Neuroblastoma can be classified as low-risk, intermediate-risk, or high-risk. About half of all children diagnosed have high-risk disease, which is treated with an aggressive combination of chemotherapy, radiation therapy, stem cell transplant, and sometimes immunotherapy. Despite this intensive treatment, less than 50% of children with high-risk neuroblastoma survive, and those who do often face long-term, and potentially life-threatening, side effects from treatment.

What is ALK? Anaplastic Lymphoma Kinase, or ALK, is a protein that helps cells grow and develop, especially during early life. Typically, ALK activity is low or turned off after birth; however, in some cancers, it becomes abnormally active due to mutations or other changes, causing cells to grow uncontrollably and form tumors. In neuroblastoma, ALK mutations are found in a subset of cases and can drive cancer growth. However, the native (normal) ALK protein is present on the surface of neuroblastoma cells in the majority of patients, as well as some subsets of other pediatric and adult cancers, making it a promising and widely applicable target for immunotherapy.

What are ADCs? Antibody drug conjugates, or ADCs, are an emerging class of cancer therapies that combine the targeting ability of monoclonal antibodies with the potency of powerful cancer-fighting drugs. The antibody portion of the ADC recognizes and binds to a specific protein on the surface of a cancer cell. Once the ADC is bound, it is taken into the cell where it releases the drug payload to kill the cancer cell from within. This approach allows for precise delivery of the drug to the cancer cells while minimizing damage to healthy cells.

What is the goal of Dr. Mossé’s work? Dr. Mossé and her team have developed an ALK-specific ADC, which has shown strong and sustained tumor shrinkage in preclinical models of neuroblastoma. In her CureSearch-funded work, she will further refine this novel therapy and assess its safety and efficacy in the lab. Through these studies, she will identify a lead candidate for further clinical development and complete preclinical studies that will support the initiation of a clinical trial in children with high-risk neuroblastoma at the end of her award period.

What is the potential impact of this project? This project will support the development of the first ALK-specific ADC and expedite its path toward clinical testing. Because the native ALK protein is present on the majority of high-risk neuroblastoma tumors, this therapy has the potential to benefit most patients with this aggressive disease and may also be effective in other pediatric and adult cancers. This work represents a novel application of ADCs in pediatric cancer and a potential paradigm shift in a field where innovative treatments are desperately needed. The results will lay the foundation for a future clinical trial in children with high-risk neuroblastoma, bringing a potentially curative treatment to currently incurable patients.