Grants Search Results

Lymphoma is the most common cancer in adolescents and young adults (AYA) (15-30 years) and the third most common cancer in children (C) under the age of 15 years (CAYA). This childhood, adolescent and young adult lymphoma cell therapy consortium brings together 8 multidisciplinary academic centers to facilitate targeted cell based translational research in poor-risk and rare lymphomas. This project will likely increase long-term complete remissions, decrease late effects and secondary cancers, reduce health care expenditures and provide a strategy for similar targeted cell based therapy strategies for CAYA patients with poor-risk lymphomas and other similar malignancies. Funds administered by New York Medical College.  

This grant is named for Markit, Ltd. whose 24-hour head-shaving events worldwide have raised over $2.2 million since 2007 to fund life-saving research through the St. Baldrick’s Foundation.

Based on progress to date, Dr. Chang was awarded a new grant in 2013 to fund an optional third year of this fellowship. Children with Neurofibromatosis Type 1 (NF1) are strongly predisposed to Juvenile Myelomonocytic Leukemia (JMML), a relentless form of cancer. Only 50% of children with JMML survive beyond 5 years, and hematopoietic stem cell transplantation currently offers the only potential for cure, although transplant-related mortality is high. Therapies targeted to specific molecular abnormalities in JMML may offer a better alternative. Ras is a protein involved in normal cellular growth as well as malignant transformation. Understanding the therapeutic effects of inhibiting Ras effector pathways will inform novel treatment strategies.

Cancer is caused by alterations (mutations) in the genetic material of tumor cells. The identification of these mutations has allowed the development of treatments specifically targeted at the mutated genes, resulting in remarkable clinical advances for a few specific cancer types. This proposal uses state-of-the-art sequencing technologies to analyze hepatoblastoma, the most common liver cancer of children. The goal of this project is to dramatically shift current research and treatment paradigms by directing investigators to the most relevant genes causing hepatoblastoma, which are currently largely unknown.  

Diffuse Intrinsic Pontine Glioma (DIPG) and Medulloblastoma (MB) are the two most common malignant brain tumors in children, highly aggressive tumors that cause disability and death. A new concept in cancer biology is the cancer stem cell hypothesis, which states that tumors are initiated and maintained by a small fraction of cells with stem cell-like properties. This hypothesis could explain many of the mysteries of cancer biology, one of them being the recurrence of the same tumor despite aggressive radiation and chemotherapy. This study uses a computer program called MiDReg with DIPG and MB tumor samples to learn more and ultimately develop safer and better treatments.

Based on progress to date, Dr. Chow was awarded a new grant in 2014 to fund an additional two years of this Scholar award. High-grade gliomas (HGGs) are aggressive brain tumors in children, extremely difficult to treat. Current therapies are ineffective and the majority of patients succumb to their disease, with HGG responsible for a significant portion of cancer-related deaths in children. To date, the majority of research on HGG has been conducted on tumors in adults, but there is evidence that HGGs in children have different characteristics, which suggests that treatments for adults may not be effective in children. This study is to better understand how HGGs arise and grow in children in order to tailor treatment to this population and identify combinations of drugs that will improve survival.

The International Neuroblastoma Risk Group (INRG) Task Force has collected data on over 11,500 children with neuroblastoma. These data are available to researchers from around the world, and seminal discoveries have already been made using this unique collection of patient data. However, the current application housing the INRG data has significant limitations, and this project develops tools to overcome those. The INRG has recently reported racial disparities in outcome in neuroblastoma, and studies indicate genetic factors contribute to the poor outcome seen in the black cohort. Banked DNA samples will be identified and used to learn the variables contributing to these disparities. The goal of the Interactive INRG database is to transform neuroblastoma research by enabling studies on large international cohorts of patients never before possible. Funds administered by the University of Chicago.  This grant is generously supported by the “Just Do It…and be done with it” Hero Fund created in honor of Sara Martorano and celebrates the courage of all kids with cancer through treatment and the support of their family and friends.

The intensive chemotherapy that is required to treat pediatric acute myelogenous leukemia (AML) results in prolonged periods of extremely low white blood cell counts, which in turn is associated with a significant risk of death from infectious complications. In fact, treatment related mortality is as high as 20% in adolescents and young adults undergoing chemotherapy for AML. This study aims to test potential new therapies that can help overcome the low white blood cell count (neutropenia) that results from intensive chemotherapy, to reduce the risk of infectious complications. Funds administered by Fred Hutchinson Cancer Research Center.

A growing tumor requires a blood supply, and in some tumors, such as neuroblastoma, the number of blood vessels in a tumor correlates with metastases and mortality. The formation of new blood vessels is called angiogenesis. Anti-angiogenic drugs designed to stop these blood vessels from forming have proved disappointing, so far. The lab in which Dr. Elster is working has identified one reason for this. In this project, known pharmacologically active compounds are screened to find what may be the backbone for the next class of anti-angiogenic drugs.

T-cell acute lymphoblastic leukemia is an aggressive cancer that requires highly intensive chemotherapy, and the prognosis of patients with relapsed and refractory T-ALL is very poor. The genetic lesions responsible for progression and relapse in this disease remain largely unknown. The goals of this project are to identify novel pathogenic genes and pathways in relapsed and refractory T-ALL, to assess their contribution to T-cell transformation and chemotherapy resistance. These results will be ultimately translated in new diagnostic tools to identify high-risk patients and in new molecular targeted drugs for the treatment of this disease.

Viruses promote many cancers. The first human tumor virus, Epstein-Barr virus (EBV), was discovered in cells of a child with Burkitts lymphoma. Since that time, EBV has been detected in several cancers - particularly of children and adolescents. To greatly diminish the risk of cancer, particularly in high-risk youngsters, this study works on the development of a vaccine that stimulates a robust immune response and blocks EBV infection and/or limits spread within the body, preventing tumor development or the likelihood of recurrence. A recent VLP vaccine has proved highly successful in preventing HPV infection and cervical cancer in young adults. EBV is far more complex, but Dr. Fingeroth is working to creatively modify this unique technology to develop a safe and effective vaccine that protects children and adolescents from EBV-associated malignancies.  

Several recent studies have identified point mutations IDH1 and IDH2 in gliomas. IDH are key enzymes involved in cell metabolism. These mutations occur frequently (50-93%) in diffusely infiltrating astrocytomas and oligodendrogliomas, as well as in some glioblastomas. These studies suggest that IDH1 mutations are an early event in the formation of specific types of diffusely infiltrating gliomas, and this project uses a virus to deliver genes to determine if mutant IDH1 can induce brain tumors in models.  

Acute myeloid leukemia (AML) is the second most common leukemia in children, with only about a 50% long-term survival. Among the new agents developed during the last decade, histone deacetylase (HDAC) inhibitors (HDACIs) have shown great potential for the treatment of children with AML. It has been shown that HDACIs can significantly enhance the effectiveness of the main drug used for treating children with AML, but the detailed molecular basis underlying that process is unknown. The goal of this study is to form a solid base for establishing new effective therapies for treating children with AML.  

Based on progress to date, Dr. Gershon was awarded a new grant in 2014 to fund an additional two years of this Scholar award. Medulloblastoma strikes the cerebellum, a brain region that sees rapid growth after birth, as special cells called progenitors divide repeatedly, increasing the number of brain cells. Gene mutations that allow unrestricted progenitor growth cause medulloblastoma. Understanding which genes control progenitors, and how these genes work together, may lead to new medulloblastoma treatments. Dr. Gershon is investigating a previously unknown connection between the immune system, brain growth, and the formation of brain tumors, and a novel way to use developmental biology to treat medulloblastoma.  

While significant progress has been made in the treatment of acute lymphoblastic leukemia (ALL), there remain specific anatomical sites into which leukemic cells infiltrate and become very resistant to traditional therapies. One of these sites, the central nervous system (CNS), is particularly challenging to treat. Preliminary studies have identified specific cell types in the CNS that contribute to tumor resistance to treatment. The goal of these studies are to expand this knowledge to contribute to the design of new therapies optimized to meet this important clinical problem.  

Rhabdomyosarcoma (RMS), a malignancy arising from striated muscle, is the most common soft tissue sarcoma in children. Metastatic RMS has a poor prognosis and the different subtypes of RMS vary in their clinical behavior. Epigenetic mechanisms may play a role in the progression or differentiation of RMS, but this has not been well studied in this disease. This project uses a novel assay that has revealed important genetic therapeutic targets in other malignancies. It has the potential to advance understanding and help discover new prognostic or therapeutic targets in RMS.  

Neuroblastoma is the second most common solid cancer in childhood. Half of patients are at an advanced stage at diagnosis, difficult to treat successfully even with aggressive therapy. Ferritin is the body's storage form of iron, and elevated levels have been linked to worse outcomes in patients with neuroblastoma, but this phenomenon is still poorly understood. This research is investigating how genetic mutations in HFE, the gene responsible for the iron overload disorder, promote the development and spread of neuroblastoma cells. By identifying which specific iron metabolism pathways are involved, we can come up with new therapeutic strategies that are more specific and less toxic.

Based on progress to date, Dr. Kim was awarded a new grant in 2014 to fund an additional two years of this Scholar award. Despite the recent advances in chemotherapy for acute lymphoblastic leukemia (ALL), drug resistance often results in relapse of ALL. Preclinical studies have shown that leukemia cells can evade chemotherapy as they are protected by their bone marrow environment. This study proposes to dislodge chemo-resistant cells from the protective bone marrow making them vulnerable to chemotherapy. We propose to study the functional role of CD49d in drug resistant leukemia and will validate it as a potential, novel target for treatment of recalcitrant childhood ALL.

This research involves primitive neuroectodermal tumors (PNETs). One type of PNET, medulloblastoma, is the most common pediatric brain tumor, but current treatments are limited and often have severe side effects, including lifelong cognitive impairment. A common event leading to PNETs is when cells accumulate too much of a certain gene called N-Myc. Surprisingly, we still do not know how too much N-Myc causes these childhood cancers, but there are clues that excess N-Myc alters DNA structure in normal stem cells of the brain leading them to become cancerous. This research tests this idea by determining how N-Myc acts on DNA in stem cells of the brain leading to medulloblastoma, providing the foundation for new treatments, which are both safe and effective. Because N-Myc is implicated in all PNETs including neuroblastoma, retinoblastoma, and Wilms tumor, these studies have extremely high impact and clinical significance.

Myelodysplastic syndrome (MDS) is a blood cancer that affects the bone marrow stem cell and may lead to acute leukemia. Pediatric MDS is rare and causes are unclear, although associations exist with inherited bone marrow failure syndromes. Diamond-Blackfan anemia (DBA) and Shwachman-Diamond syndrome (SDS) significantly predispose to MDS and are linked with disruption of an important organelle in the cell called the ribosome. This new consortium of clinical and basic researchers is studying the biology of pediatric MDS associated with ribosome dysfunction. This project is directly relevant to finding therapeutic targets for MDS, a devastating and understudied form of blood cancer in children. Funds administered by the Feinstein Institute for Medical Research.

Osteosarcomas are a devastating pediatric bone cancer for which survival rates have not improved over 30 years. Current treatments remain aggressive and are prone to relapse. A new gene has been identified called Sox2, upon which osteosarcoma cells depend for survival. This project will evaluate whether strategies for blocking Sox2 function in tumors can eradicate the tumor and all residual cells to prevent relapse of the disease. These studies provide a novel basis for the targeted treatment of this childhood cancer and lead to a better understanding of the cancer stem cells that give rise to tumors.