The All-Star Grant is a re-investment in previous V Scholar or Translational grant recipients who are invited to apply for a $1,000,000 grant payable over 5 years. Any type of cancer research is permitted. This grant also includes salary support for a mentored post-doctoral fellow, which supports the next generation of cancer researchers.
Co-funded by the Dick Vitale Pediatric Cancer Research Fund and the Jeff Gordon Children’s Foundation
What big question(s) will your work answer? Rhabdomyosarcoma is a deadly cancer that occurs in children and young adults. Several decades of research points to a specific molecule (called PAX3-FOXO1) as the most compelling drug target in this disease. However, we simply do not understand the molecular details of PAX3-FOXO1 enough to made a medicine that exploits this target. The big question addressed in this project will be to understand this compelling target with atomic detail by applying innovative technology. • Why does this question matter? Children continue to die of rhabdomyosarcoma and yet the medicines used in the clinic are woefully inadequate and toxic. A new therapy tailor-made for this disease could change everything. • How will your work answer the big question? Our work has the potential to provide a basic science foundation upon which a drug discovery campaign could be launched.
Co-funded by the Dick Vitale Pediatric Cancer Research Fund and the Jeff Gordon Children’s Foundation
Children with cancer are typically treated with chemotherapy to kill all dividing cells, including tumor cells. This general treatment causes side-effects, including damaging the normal healthy cells children need to grow and thrive. An additional, devastating, long-term side-effect of the use of chemotherapy is the risk of developing a second cancer. To circumvent these toxicities, we propose a targeted treatment tailored for a subset of pediatric patients with blood cancer. We identified a gene called “CUX1” that is deleted in the blood cells of patients with certain types of leukemia. Loss of one copy of CUX1 causes blood cells to grow too fast and stop maturing. In the current proposal, we predict that a drug that increases CUX1 levels will prevent leukemia growth and restore normal blood cell maturation. The objectives of the current proposal are to identify druggable regulators of CUX1 and to use these compounds to restore CUX1 in leukemias with CUX1 loss. We have identified one candidate regulator, named GSK3. We hypothesize that inhibition of GSK3 will increase CUX1 levels, halt leukemia growth, and restore normal blood development. We will accomplish these studies using innovative genetic screening, novel mouse models of childhood leukemia, and patient leukemia samples. Accomplishing the proposed studies will aid in the development of non-toxic therapies for children. This work will help us achieve our long-term goal of devising urgently needed treatments to improve the outcome for high-risk leukemias of childhood.
Co-funded by the Dick Vitale Pediatric Cancer Research Fund and the Jeff Gordon Children’s Foundation
Neuroblastoma is a childhood cancer that can be difficult to treat. Currently, studies are needed to figure out effective and safe ways to treat this type of cancer. Using animal models who can develop neuroblastoma, we found a special type of cells present within the tumors that allow them to grow and spread to other parts of body. By creating our own version of these cells, we can reverse their role and block the growth of tumors instead. We are proposing to use these modified cells to inhibit tumor growth. We will perform further modification on these cells to increase their success on killing cancer cells with less or no off-target effect on normal cells in the body. Through these studies, a new way to treat this childhood cancer may be found.
Funded by the Dick Vitale Pediatric Cancer Research Fund in partnership with Mat Ishbia and Justin Ishbia
Years of cancer research have shown that combining therapies that work differently virtually always works better than when therapies are used alone. New medications are being discovered that change the way that genes are turned on and off. At this same time, treatments are also being developed that use the body’s own immune cells to find and attack cancers. Both of these treatments have been shown to work alone on specific cancers. But each have known limits. We are asking whether combining these treatments will result in a new approach to fight two aggressive cancers: Ewing sarcoma and osteosarcoma. We predict that combining these treatments will result in an effective and well tolerated therapy.
Funded by the Dick Vitale Pediatric Cancer Research Fund in partnership with Mat Ishbia and Justin Ishbia
Childhood cancer remains the leading cause of death from disease in children in high-income countries. Our lab has used cutting-edge technologies to hunt for new drug targets in high-risk pediatric cancers. In neuroblastoma, a common pediatric solid tumor, we discovered a new potential therapeutic target. Drugs have been developed against this target, but they have not been tested in neuroblastoma. In this proposal, we will perform the critical testing of these drugs in high-risk neuroblastoma models in the lab. We will also determine why neuroblastoma cells depend on this target for survival. It is our long-term goal to develop clinical trials testing these drugs in children with high-risk neuroblastoma.
