Alex's Lemonade Stand Foundation for Childhood Cancer

Medulloblastoma (MB) is the most common malignant brain tumor in children. Although treatments like surgery, chemotherapy, and radiation can control the disease, they often come with serious long-term side effects. For children whose tumors carry a mutation in the p53 gene—a gene that normally helps prevent cancer—treatment is even more difficult. These p53-mutant tumors are more likely to return after therapy, and there are currently no effective treatments for relapse. One promising idea is to force cancer cells to enter a state called senescence, where they stop growing but don’t die.

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.

Diffuse midline gliomas (DMGs) are one of the deadliest forms of childhood cancer. Most children with DMG die within a year of being diagnosed with the disease. Immunotherapy with anti-GD2 CAR T cells extended survival in mouse models and induced tumor shrinkage in a pilot study in DMG patients. However, tumors inevitably recurred and caused patient death, pointing to the need for strategies that enhance response to therapy.

Neuroblastoma is a childhood cancer that forms from the developing nervous system. Like many cancers, there is a wide range of long-term outcomes for neuroblastoma. For patients diagnosed with high-risk disease, treatment is intensive and includes surgery, chemotherapy, and radiation. Despite this aggressive treatment, approximately one half of all high-risk patients are not cured by current approaches. Many high-risk, treatment resistant tumors demonstrate activation of the MYCN gene. There is a gap in our ability to treat cancers driven by MYCN.

Mentor Name: Zulekha Qadeer