Grants Search Results

Each human cancer is driven to be lethal by a different set of tumor specific genetic changes. Discovery of these mutations is leading to new targeted therapies, treatments to neutralize these genetic changes. This research involves a single mutant gene (EWS/FLI1), which is present, in some form, in all Ewing Tumors. In addition to learning more about a particularly critical target of this mutant gene, Dr. May also tests one approach to targeted combination therapy, which could be quickly moved to clinical trials.

Neuroblastoma can range from spontaneous regression to relentless progression. Clinical and biological prognostic factors are used to classify patients as low-, intermediate-, or high-risk of relapse, to determine the intensity of treatment necessary. Recently, several investigators have published "genetic signatures" that correlate with outcome in children with high-risk neuroblastoma in retrospective studies, but due to expense, timing and availability, these signatures are not currently used. This project aims to circumvent these limitations, improving the care of the 40% of high-risk patients who are destined to fail current therapies. Awarded at The University of Chicago and transferred to Dana-Farber Cancer Research Institute. 

Based on progress to date, Dr. Mullighan was awarded a new grant in 2014 to fund an additional two years of this Scholar award. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and still the most common cause of cancer related death in children. This project uses cutting-edge genetic profiling approaches to identify all genetic alterations contributing to the pathogenesis of high-risk childhood leukemia. This project uses detailed genomic analysis coupled with the development of experimental models of ALL that examine the role of newly identified genetic alterations in the development of leukemia, and response to therapy.  

Medulloblastoma is the most common malignant brain tumor in children; despite advances in neurosurgery, radiotherapy, and chemotherapy, children with high-risk medulloblastoma have a 5-year survival of only 25%. Effective tools for diagnosing, staging, and monitoring are critically needed for these children. MRI is the current state-of-the-art anatomical imaging modality. PET imaging does not work well in brain tumors. Dr. O'Dorisio is developing a new PET imaging agent that will work well in brain tumors. Using PET and MRI together will help determine when children are responding with the goal of decreasing the amount of radiation therapy for many children with medulloblastoma.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and a leading cause of cancer death in children. The gene HMGA1 causes normal cells to transform into leukemia cells, and blocking HMGA1 kills leukemia cells. Other genes cooperate with HMGA1 to cause leukemia. Dr. Resar is studying agents that block these genes and could be adapted for use in therapy. The goal of these studies are to provide a paradigm for treatment of ALL with microRNA replacement therapy and other small molecules, with plans to translate successful studies to the clinic to improve outcomes for children with ALL.  

Neuroblastoma is the second most common solid cancer in children, and only 45% with high-risk disease are cured. The goal of the New Approaches to Neuroblastoma Therapy (NANT) consortium is to develop and test new therapies with high potential for improving survival. NANT links laboratory and clinical investigators to develop therapies that are tested at 16 North American neuroblastoma centers. Studies are supported by the NANT Operations Center at Children's Hospital Los Angeles. Studies test two new ways to improve elimination of small amounts of tumor cells that remain after high-dose chemotherapy. Funds administered by Children's Hospital Los Angeles.

The inherited bone marrow failure syndromes (IBMFS) are a group of disorders characterized by cancer predisposition. The study of these rare disorders has historically yielded critical insights into universal molecular pathways that cause cancer in the general pediatric population. A common feature of many of the IBMFS is impaired ribosome production or function. Ribosomes were thought to have only a housekeeping role in cells, but recent studies show that alterations in protein translation resulting from ribosomal abnormalities can promote cancer formation. There is an urgent need to better understand this connection. This project evaluates how changes in ribosome function alter protein translation to promote pediatric cancer formation.

The risk of relapse in non-Hodgkin lymphoma (NHL) patients could be related to the ability to completely kill all NHL cells in the body. An international intergroup (US and Europe) non-Hodgkin lymphoma (NHL) treatment trial for children and adolescents will be open at Children's Oncology Group (COG) sites. This study aims to determine if remaining lymphoma cells (residual disease) have been killed, which requires special techniques.  

Leukemia, a cancer of the white blood cells, is the most common cancer in children. While a majority can expect to be cured with chemotherapy, a significant number either never go into remission, or relapse. One theory as to why certain leukemias do this is that normal, non-cancerous cells in the bone marrow can help small populations of leukemia cells evade chemotherapy-induced death, leading to relapse. This research project focusing on a protein called CXCR4, is to find a way to make chemotherapy more effective and may lead directly to clinical trials in children with high-risk leukemias that will improve cure rates.

Based on progress to date, Dr. Skiles was awarded a new grant in 2013 to fund an optional third year of this fellowship. Vincristine is one of the core anticancer agents used in many childhood cancers. It is associated with cumulative dose-dependent neurotoxicity, often making it necessary to reduce chemotherapy dosage, compromising effective treatment. There is substantial variability in the way vincristine is metabolized from one person to the next. For example, Caucasians develop neurotoxicity much more frequently than African-Americans, probably as a result of genetic differences in a specific drug-metabolizing enzyme. This is of particular importance in African populations where the treatment outcome is poorer than in U.S. populations. Currently, drug dosing recommendations used in Kenya are based on dosing schemas derived in primarily Caucasian patient populations. This study helps develop individualized vincristine dosing parameters based on genetic predictors, which may lead to improved cure rates, as well as less neurotoxicity in long-term cancer survivors both in the U.S. and in Kenya.

Bone marrow transplantation is an important and potentially curative treatment for children with relapsed leukemias. Infections due to a delay in the recovery of the immune system after transplantation are a major cause of complications and even death in these children. T-cells are a type of immune cells that fight infection. Of the various components of the immune system, the T-cells are the one that recover the poorest after bone marrow transplantation. The aim of this project is to understand how VEGF improves T cell production, with the ultimate goal of improving cure rates for children with relapsed leukemias.

Based on progress to date, Dr. Wei was awarded a new grant in 2014 to fund an additional two years of this Scholar award. Dr. Wei and his team are using a genetic screen to study a novel candidate drug molecule's mechanism of action as an inhibitor of NAMPT, a key protein that regulates cancer cell metabolism. Their findings show that the molecule is effective against patient leukemia cells. Dr. Wei is working to better understand how this molecule works to kill leukemia cells and identify what are the genes and pathways involved, in hopes that it can be used to treat and cure patients with acute lymphoblastic leukemia.

MicroRNAs are small regulatory molecules that play important roles in tumor formation. Retinoblastoma (RB) is the most common malignant tumor of the eye in childhood cancer. The role of microRNAs in RB remains unclear, but a group of microRNAs that are highly expressed in the early embryonic retina and known to promote cellular proliferation and survival and cancer formation, are highly expressed in RB cells. These miRNAs may be novel therapeutic targets for the treatment of RB. If so, this project could define new therapeutic targets for treatment of RB and may also have important implications for other types of pediatric tumors.

Dr. Yu has recently reported a major breakthrough in the treatment of neuroblastoma with anti-GD2 antibody and cytokines, but the treatment is accompanied by serious side effects including allergic reaction. This project is to test a possible reason for this reaction, using blood samples from patients enrolled in the immunotherapy trials for measurement of anti-sugar antibodies. If the hypothesis is proven true, this research could provide a direction for reducing the toxicities and further improving the outcome of this highly successful immunotherapy.

This grant is for Pediatric Cancer Genomics (PGen), a research conference planned for February 2012. Attending will be leaders in national and international translational cancer genomics, to focus on pediatric solid tumors including neuroblastoma, medulloblastoma, Wilms tumor, osteosarcoma, Ewings sarcoma, rhabdomyosarcoma, and rare cancers striking adolescents and young adults. Topics will include next generation sequencing, functional genomics, translation, personalized molecularly directed therapy, biology, bioinformatics, and more. The meeting will be hosted by Translational Genomics Research Institute in Phoenix, Arizona and is being co-sponsored by the St. Baldrick's Foundation with the QuadW Foundation.

Based on progress to date, Dr. Raabe, the Hannah's Heroes St. Baldrick's Scholar, was awarded a new grant in 2014 to fund an additional two years of this Scholar award. Medulloblastoma is the most common malignant pediatric brain cancer, and patients with high-risk medulloblastoma have a poor prognosis. Unfortunately, few models for aggressive medulloblastoma exist, severely limiting our ability to test new treatments for the patients who need them most. The goal of this proposal is to develop accurate models of high-risk medulloblastoma for pre-clinical therapeutic testing. This allows for rapid progress to be made, as researchers can use these models to screen for new drugs, test drug combinations, identify for factors conferring resistance to chemotherapy, and look for pathways that might be an "Achilles heel" for high-risk medulloblastoma.

This grant is named for the Hannah's Heroes Hero Fund created in honor of Hannah Meeson and pays tribute to her fight by raising awareness and funding for all childhood cancers.

Sarcomas are aggressive cancers that arise in connective tissues such as skeletal muscle. Approximately 12,000 Americans are diagnosed with sarcoma each year, including a large number of children and adolescents. Even with the most advanced therapies, about half of all sarcoma patients will die from their disease. With past St. Baldrick's support, Dr. Hettmer has identified a subset of genes that are present at increased levels in sarcomas and may serve as new candidate drug targets for these cancers. This project builds on that work, providing essential pre-clinical data on new potential sarcoma therapies, greatly facilitating the ultimate development of treatments for current and future sarcoma patients. Dr. Hettmer is funded by P.A.L.S. Bermuda with funds raised through the St. Baldrick's Foundation.

Resistance to chemotherapy is a great challenge in the cure of cancer. A large proportion of such resistance occurs because of p53 mutations in the tumor, the most commonly occurring mutation in cancer. Dr. Kupfer's research involves a virus that appears to cause resistant p53 mutant cells containing a particular protein to become sensitive to chemotherapeutic drugs. A large library of small molecules will be screened to identify a substance that can mimic this effect, with the ultimate goal of developing a drug that can overcome resistance to chemotherapy.  

Lymphoblasts infiltrate the central nervous system (CNS) in about 30% of children and adolescents with acute lymphoblastic leukemia (ALL), leading to relapse in the brain and spinal cord. While aggressive CNS therapy involving high-dose chemotherapy with radiation has been successful, many patients have significant problems with long-term effects, including a much higher risk of a second cancer and long-term deficits in cognitive function and development. This research is to discover unique aspects of the biology and pathogenesis of leukemia, with a goal of finding new therapeutic targets that can be tested in future clinical trials.  

Because of low patient numbers at individual centers, meaningful clinical research in pediatric hematopoietic stem cell transplantation (HSCT) requires collaborative, multi-institutional studies with a large number of relatively small centers. In 2009, the St. Baldrick's Foundation awarded a grant to the Pediatric Blood and Marrow Transplant Consortium (PBMTC) to construct a clinical trials infrastructure that would allow high-quality, appropriately monitored, multi-center pediatric trials. This grant continues funding for these important pilot trials to increase safety for pediatric patients after transplant, reduce relapse by giving immune therapy before and after transplant to leukemia patients, and explore the feasibility of new cellular therapy approaches aimed at preventing relapse. Funds administered by the National Marrow Donor Program.