Grants Search Results

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.

Ewing sarcoma (ES) is one of the most common sarcomas in children, caused by a genetic abnormality called a "chromosomal translocation." This study has two goals. First, to understand the normal function of the protein EWS, to learn about what goes wrong in Ewings tumors. Second, to understand what other genetic events are required to turn normal human cells into Ewing sarcomas. Our approach is to try to combine EWS/FLI-1 expression with other genetic events in the type of human cell that we know gives rise to ES.

This grant is to the New Approaches to Neuroblastoma Therapy (NANT) consortium, 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 15 North American neuroblastoma centers, supported by the NANT Operations Center at Children's Hospital Los Angeles. The strategy includes accurately evaluating response with "biomarkers" for tumor cells in blood and bone marrow combined with sophisticated imaging of tumors, essential for "personalized treatment" to predict if the treatment will benefit the patient. NANT studies enable definitive testing later in larger patient numbers. Funds Administered by the Children's Hospital Los Angeles.

While current therapies have greatly improved the overall survival of children with leukemia, patients with acute myeloid leukemia (AML) still have a poor outcome. This research focuses on determining the role played by the CALM gene in the onset of leukemias. These studies improve our understanding of how CALM-rearranged leukemias develop and contribute to the development of novel therapeutic strategies to fight childhood leukemias.

The goal of this proposal is to identify tumor suppressor genes that are "turned off" by DNA methylation and contribute to the formation of Ewing Sarcoma, a type of bone cancer that affects teenagers and young adults. This study searches for a better understanding of Ewing Sarcoma and the development of better treatments.

Cancer is a disease caused by mistakes in the DNA of tumor cells. Identifying all these mistakes in a single type of cancer has been slow, but understanding them will revolutionize the way cancer is diagnosed and treated. This project makes use of exciting new developments in "sequencing technology" to identify all the DNA mistakes in neuroblastoma. This is the very first such effort ever undertaken for a pediatric cancer, and leverages the support and expertise of investigators at Children's Hospital of Philadelphia, the Children's Oncology Group and Johns Hopkins University.

Pleuropulmonary blastoma (PPB) is a rare but biologically important lung cancer of young children. Recently identified inherited genetic mutations predispose children to developing PPB, leukemia and other childhood tumors arising in the muscle, brain, ovary and kidneys. To understand how these tumors form and progress, this research uses models based upon genetic discoveries in families with hereditary PPB, by identifying the cellular events responsible for PPB initiation and progression. This is an essential step toward developing ways to detect, treat and improve outcomes for children with PPB and the related tumors associated with this inherited cancer predisposition syndrome.

This grant funded a cutting-edge research project to find new and better cures for childhood cancer.

This grant funds a cutting-edge research project to find new and better cures for childhood cancer.