Childhood Cancer Research
Children’s Hospital of Philadelphia
3401 Civic Center Boulevard
Philadelphia, PA 19104
United States
Neuroblastoma is a devastating childhood cancer that is responsible for ~12% of childhood cancer mortality in addition to significant morbidity among survivors. Better approaches to treating this disease are desperately needed. One of the most important causes of neuroblastoma is when the levels of a gene called MYCN get extremely high in specific cells. This helps change normal cells into cancer cells and then helps the cancer cells grow and spread. Because of this, scientists are trying to make drugs that specifically block MYCN and have made important advances.
Pediatric brain and spinal cord tumors are the deadliest form of childhood cancer. Diffuse midline glioma (DMG) stands out among these tumors as a particularly devastating disease that arises in the center of the brain at a median age of 6 years old. These central areas of the brain are important for our basic functions, so tumors in these locations cannot be surgically removed. Unfortunately, despite decades of clinical trials with radiation and chemotherapy, we have made little to no progress for patients with DMG.
Children’s Hospital of Philadelphia
Children’s Hospital of Philadelphia
Childhood cancers are caused by genetic mutations that lead to changes in proteins that are essential for normal human development. The protein MYCN is the cause of many of the most aggressive pediatric cancers, including high-risk neuroblastoma and medulloblastoma. One of the holy grails of pediatric cancer drug development is finding a way to directly target MYCN in patient tumors, but this has been elusive. To address this major unmet need, we have developed an international team of scientists with complementary expertise to attack this problem with innovative new technologies.
The job of the immune system is to fight infection. In healthy people the immune system also prevents cancer. Recently, new cancer treatments using the immune system have been made. These new treatments are called chimeric antigen receptor T-cells (CART). With CART, blood immune cells are collected from a patient. They are reprogrammed in a laboratory to fight cancer. The reprogrammed cells are given back to the patient. CART can cure some cancers. CART is particularly good at curing a type of cancer called B-cell acute lymphoblastic leukemia (B-ALL) in kids.
Neuroblastoma is an aggressive cancer of the developing nerves that occurs in young children. There has been little improvement in the prognosis of children diagnosed with high-risk neuroblastoma over the last few decades. Recent advances in the field of cancer immunotherapy (using the immune system to combat tumors) have resulted in unheralded enthusiasm for the use of this potent treatment to fight against neuroblastoma. However, we desperately need new molecules and novel approaches to safely and most effectively target neuroblastoma cells with the immune system.
This project seeks to develop a new immunotherapy for children with relapsed neuroblastoma and medulloblastoma. These cancers of young children arise in the peripheral and central (brain) nervous systems, respectively, and have many common features that make them so aggressive and difficult to cure. Both are currently treated with very intensive chemotherapy and radiation therapy that are far too often ineffective, and even when cure is achieved, patients suffer lifelong disabilities directly related to their therapy. New therapeutic approaches are desperately needed.
Menin inhibitors are a new class of drugs that has shown great promise for the treatment of certain highly aggressive leukemias in children. However, there are many patients in whom the drug does not work. We have developed a strategy of combining Menin inhibitors with a second class of drugs called LSD1 inhibitors to improve efficacy and overcome resistance.
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