Funded by the Dick Vitale Pediatric Cancer Research Fund with support from the Glover and Frazier families
T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL) are types of blood cancer that are very hard to treat. Patients with these leukemias need to get strong chemotherapy that can have bad side effects. Because of this, we need to find new treatments that are less toxic. CAR T-cell therapy is a new type of treatment that uses the patient’s own white blood cells and allows them to detect and kill cancer cells. These therapies can focus on only killing the cancer cells and not normal tissues and have few side effects. We have invented a way to treat this type of leukemias and have shown that it works well in models in the laboratory. We want to find out if our CAR T-cells are safe and effective in patients with childhood T-ALL/LBL. To help us reach our goal, we have formed a group of experts, including a) Lab experts – who design CAR T-cells, b) Clinical experts -who know how to treat leukemias c) Immunology experts – who can tell us how the CAR T-cells work and d) Pathology experts – who can study how the leukemias respond to the treatment. Our hospital has what is needed to start the clinical trial that we are planning. We want to find a cure for T-ALL/LBL that has few side effects and help save the lives of children with this type of leukemia.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Osteosarcoma is the most common bone cancer of children. When this cancer recurs in the lungs, we have no effective therapies for these patients, and they continue to be treated with the same drugs that have been used for the past 40 years. This work seeks to develop new treatment options for patients with recurrent osteosarcoma. We will use dogs, a natural model of this cancer, to test a new drug combination which uses the immune system to stop osteosarcoma growth. We will also use advanced monitoring techniques to determine which patients benefit from this new treatment. Testing these drugs in dogs will inform how best to use these new therapies for human patients with osteosarcoma. Importantly, it uses drugs which are also readily able to be used in human patients, thus having the potential for rapid movement to the clinic.
Black patients are more likely to die from breast, prostate, lung, and colorectal cancers than White patients. There are many reasons for these differences, including difficulty receiving life-saving treatment. New treatments that match the type of cancer a patient has to specific drugs have been developed and has changed the way we treat the disease. The first step to getting these new treatments is for patient’s tumors to be tested for specific changes. However, Black patients are less likely to receive these tests and to receive the relevant treatment. If progress is not made in improving access to testing, Black patients will continue to have lower access to these lifesaving treatments, causing even bigger differences in survival. In this study, we will develop a program to understand the needs of Black cancer patients and provide support to ensure that they receive appropriate tests and treatment. To help design the program, we will interview Black patients and healthcare providers on what the needs are and provide navigation support to patients. We will measure how effective the program is in increasing testing and treatment among Black patients. In the future, we hope to use this data to develop broader strategies that will improve Black patients’ access to tests, clinical trials, and treatment.
Funded by Kay Yow Cancer Fund 2023 Final Four Research Award
One of the greatest challenges in cancer treatment is that response to standard treatment is frequently incomplete and causes many side effects. Current treatments are often ineffective because they function as a “one-size-fits-all” approach to a very personal disease. This lack of success is magnified in triple negative breast cancer (TNBC), which differs greatly between each individual. We have recently discovered a protein that is not expressed anywhere in females, except in TNBC tumors, where it is required for tumor growth. This protein is normally only found in male testes. Thus, this protein is a perfect target to inhibit tumor growth without impacting normal tissues. Here we will study the function of ZNF165 and determine how it promotes growth of tumors. Ultimately, this work could lead to a tailored approach for treating TNBC without harming the patient.
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.
Ovarian cancer (OC) is the most lethal gynecologic cancer in the US. Unfortunately, the majority suffer relapse. Patients with recurrent platinum-resistant OC respond poorly to chemotherapy.
Immunotherapy with immune checkpoint inhibition (ICI) has emerged as a promising therapy in several cancers. Unfortunately, only small fraction (10-15%) of patients with OC do benefit from immunotherapy. Therefore, effective strategies are warranted to improve the overall benefit of immunotherapy in OC. Targeting immunosuppressive factors within the tumor immune microenvironment (TME) represents an attractive approach. Our focus in this proposal is on tumor-associated macrophages in OC.
Macrophages with a specific ‘suppressor’ phenotype (M2 subtype) within TME play a significant role in promoting an immunosuppressive environment and in mediating therapy resistance. These cells are the most prominent cells in OC. However, another phonotype (M1 subtype) provides a favorable pro-inflammatory TME and enhances the immune response. Targeting macrophages and switching their phenotype from M2 to M1 is potentially promising approach that has not been investigated thoroughly before. In this study, we propose to target them with two strategies: Targeted inhibition of the transforming growth factor-beta (TGF-beta) receptor and CD47 inhibition.
