Grants Search Results

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.  

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.

Neuroblastoma is a cancer that develops in the nervous tissue and most cases occur in children younger than two years old. For patients with high-risk disease overall survival remains poor, thus there is a tremendous need to develop new treatments. This research improves the clinical development of a new drug, MLN 8237, which has shown promise in early pediatric clinical trials, and could improve survival in this devastating disease and provide additional targets for therapeutic intervention.

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.  

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, and relapsed ALL is the most common cause of death in children with cancer. The goal of this research is to use technical breakthroughs in human genomics to discover the underlying biological pathways involved in relapse. These discoveries will also potentially inform future treatment studies. Dr. Hogan was a St. Baldrick's Fellow and now has a faculty position.

Most cancer therapies have significant toxicity, thus new treatment strategies are needed. Pediatric patients with cancer are excellent candidates for immunotherapy because their immune system is more robust compared to adults. Due to our lack of understanding of how to best activate these specialized anti-cancer cells, progress in pediatric immunotherapy has lagged behind. This research focuses on how we can best activate specific T cells to defend the immune system against tumors, specifically gliomas (brain tumors) and advances the field of immunotherapy as a promising form of treatment for these children.

Rhabdomyosarcoma is the most common cancer that originates in the soft tissue of the body in children. There are two subtypes, embryonal (ERMS) and alveolar (ARMS), and children with ARMS have poorer response to conventional chemotherapy and radiation therapy, and much lower survival rates than those with ERMS. This research aims to discover chemical inhibitors of a gene called PAX3-FKHR and how "knocking down" that gene may help patients respond better to chemotherapy.The goal of this project is to establish a new approach for developing drugs to effectively treat ARMS.

The human body has an ability to detect and eliminate cancer through the immune system, but cancer cells can escape detection. Dr. Curran's research attempts to overcome this tumor escape via gene therapy mediated treatments. Pediatric leukemia is the most common childhood cancer, and patients with recurrent or resistant leukemia have limited options for treatment. Redirecting the immune system to eradicate resistant leukemia cells will provide a new possibility for a cure. Also, by specifically targeting cancer cells, we eliminate the long term complications associated with the conventional treatments of surgery, chemotherapy, and radiation. Dr. Curran was a St. Baldrick's Fellow and now has a faculty position.

Current therapies for neuroblastoma include the use of powerful chemotherapy, which weakens the immune system and can lead to life- threatening infections. As a result, these immune-compromised patients frequently require medication such as granulocyte colony-stimulating factor (GCSF), which helps the body produce white blood cells to help fight infection. In many adult cancers, GCSF has been found to increase the growth of cancer cells in a laboratory setting. Dr. Kim is studying how GCSF and GCSF-R enhance tumor growth, to clarify the appropriate use of GCSF in patients and determine whether GCSF- receptor may be a new therapeutic target in neuroblastoma.

Neuroblastoma is a solid tumor cancer of very young children, originating in the nerve tissue of the neck, chest, abdomen, or pelvis, but most commonly in the adrenal gland. About 45% of children diagnosed have advanced "high risk" disease, for which the survival rate is less than 40%. This project tests the new hypothesis that specific ceramide types and/or expression of sphingolipid enzymes control the growth and invasion of neuroblastoma. The role of a particular family of enzymes called ceramide synthases will also be examined. The goal is to develop new therapeutic strategies for the treatment of neuroblastoma.

Hodgkin lymphoma is a cancer of the immune system and is the most common cancer for children ages 15-19. It arises from Reed-Sternberg (RS) cells, which have two or more nuclei and often have gained or lost chromosomes. This research explores the workings of a protein called KLHDC8B, which is expressed during cell division and is altered in cases of familial Hodgkin lymphoma. Dr. Krem also uses blood and tissue samples from patients to find changes in proteins that are related to KLHDC9B. Those other proteins may be important for preventing onset of Hodgkin lymphoma.

Precursor B-lymphoblastic leukemia is a type of blood cancer in which too many immature white blood cells are found in the blood and bone marrow. It is the most common type of acute lymphoblastic leukemia (ALL). This project studies how specific B-precursor ALL cells are wired and how to disrupt this wiring by treating patients with specific and novel medications. The research improves our understanding of the biochemical mechanisms critical for the development of targeted therapies.

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,awarded in 2010, moves that project further towards its goals of: 1) increasing safety for pediatric patients after transplant by using a new medicine that has been shown in adults to treat leukemia with lower toxicity, 2) reducing relapse by giving immune therapy before and after transplant to leukemia patients, and 3) exploring the feasibility of new cellular therapy approaches aimed at preventing relapse.

Rhabdomyosarcoma, the most common soft tissue cancer in children, has two main forms; each behaves differently, so recognition is important for proper treatment. This research builds on previous studies that identified unique genes associated with one form. The proteins from these genes can be used to create special stains that are both affordable and accessible to hospitals that don't perform gene studies. This enhances our understanding of the biology of rhabdomyosarcoma, allow rapid identification of high risk patients who may benefit from specific therapies, and prevent overtreatment of patients with low risk tumors.

Pediatric patients who have bone marrow transplants have an impaired immune system, and the resulting infections can cause bacterial, viral and fungal infections and even death. Unfortunately, medicines to treat these infections are not adequate in many cases; an intact immune system is needed to achieve appropriate responses to infectious agents. The goal of this research is to expedite the immune recovery after transplant. This would result in better responses to infections and improvement in the lives and survival of patients. Dr. Stefanski was a St. Baldrick's Fellow and now has a faculty position.

A type of brain tumor called diffuse intrinsic pontine glioma (DIPG) has no known cure. Radiation therapy offers some temporary relief, but nearly all children die from this cancer within 1 year. A promising form of drug delivery, convection-enhanced delivery (CED), offers many benefits including allowing high concentration of drugs to reach the brain tumor. This study focuses on drug distribution following this new form of drug delivery. By relating drug distribution and radiation dose to tumor response, a better treatment can be designed. Resulting clinical trials for a new therapy may eventually cure DIPG.