It has been difficult to model pediatric spinal cord gliomas, which include tumors known as ependymoma and astrocytoma, by culturing the cells from patient surgeries in plastic dishes or growing them in mice. This lack of good models has in turn hindered our ability to understand which genetic changes are the key "drivers" of tumor formation and growth and how we might most effectively target these tumors with new therapies.
Project Goal
Principal Investigator Name:
Charles Eberhart, MD/PhD & Eric Raabe MD/PhD
Project Title:
Modeling Pediatric Spinal Gliomas Using Murine Spinal Neural Stem Cells
We recently sequenced Wilms tumors, a childhood kidney cancer. We discovered a novel type of missense mutation at position G1809 in the enzyme DICER1, a critical part of the microRNA biogenesis machinery. This mutation, which appears to distort the geometry of the DICER1 active site, destroys the ability of DICER1 to produce the let-7 class of tumor-suppressing microRNAs.
Principal Investigator Name:
James Amatruda, MD/PhD
Project Title:
DICER1-Driven Cancers: Models, Mechanisms and Therapies
Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and relapsed ALL is the most common cause of death from childhood cancer. Exciting new research has shown that leukemia cells depend their survival on nonmalignant, noncancerous cells in the body.
Project Goal
Principal Investigator Name:
Craig Mullen, MD/PhD
Project Title:
Targeting Microenvironmental Support of Acute Lymphoblastic Leukemia
Neuroblastoma is the most frequently diagnosed cancer in infancy and accounts for 15% of all deaths due to childhood cancers. Recent progress has been made in therapies involving antibodies that recognize neuroblastoma cells and target them for destruction. Unfortunately, many children do not respond to the antibody therapy, because the immune cells that are responsible for killing the tumor are suppressed.
Project Goal
Principal Investigator Name:
Katherine Hsu, MD/PhD & Nai-Kong Cheung, MD/PhD
Project Title:
Development of an anti-KIR3DL1 Antibody to Promote Innate Immunity Against Neuroblastoma
Patients diagnosed with "high risk" neuroblastoma have a high rate of failure (death) even after aggressive drug treatment and bone marrow transplantation leaves most children "cured". In 2010, we reported on the efficacy of an antibody therapeutic ch14.18, which reduces disease recurrence to about 25%. In 2015, after a long clinical trial, ch14.18 (renamed dinutuximab) received FDA approval and is now available to treat children. Alas, while fewer children are dying, even one death from this disease is too many, never mind 25%!
Malignant rhabdoid tumor, or MRT, is a rare but devastating childhood cancer. Most children diagnosed with MRT are under the age of two, and most will die from the disease despite intensive surgical, radiological, and chemotherapeutic interventions. A sad reality of MRT is that it is such a rare cancer that drug companies have little interest in developing new ways to treat the disease, meaning that a dismal prognosis is all we can hope to offer the two dozen children who are diagnosed with MRT in the United States every year.
Principal Investigator Name:
William Tansey, PhD
Project Title:
MYC as a Driver and Anti-Cancer Target in Malignant Rhabdoid Tumors
High-risk B-cell acute lymphoblastic leukemia (B-ALL) frequently recurs after initial treatment and is a lethal disease. "Ikaros" is a cancer fighting protein that prevents leukemia from developing. In children who are diagnosed with high-risk B-ALL, the activity of Ikaros in leukemia cells has been impaired by another protein called CK2. By using a novel medicine that can block the effects of CK2, our laboratory has found that we can restore the cancer fighting ability of Ikaros and kill leukemia cells.
Project Goal
Principal Investigator Name:
Sinisa Dovat, MD/PhD & Chunhua Song, MD/PhD
Project Title:
Targeted Combination Therapy to Sensitize High-Risk Acute Lymphoblastic Leukemia to Methotrexate via Restoration of Ikaros Tumor Suppression
Rhabdomyosarcomas are a rare but aggressive type of cancer in children and adolescents. There are approximately 350 new diagnoses of childhood RMS in the United States per year. The outcomes for high-risk patients with this disease have not significantly improved in the last several decades and survival of metastatic or relapsed disease remains extremely poor. In rhabdomyosarcoma the tumor cells resemble dividing muscle cells.
Project Goal
Principal Investigator Name:
Neetu Gupta, PhD & Peter Anderson, MD
Project Title:
Targeting the Function of Ezrin in Rhabdomyosarcoma
Hux is 7 years old and a party animal who loves dancing. Since he was diagnosed with Phelan-MCDermid syndrome at birth, he gets yearly brain MRIs - and one revealed a tumor when Hux turned 3. After a year of treatment, Hux has remained cancer-free!
