Grants Search Results

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.

Pediatric palliative care is a comprehensive system of care aimed at preventing or relieving symptoms and suffering caused by a life-threatening illness. At the end of life, hospice is an important provider of palliative care. The goal of this study is to identify factors that are associated with hospice use in pediatric oncology, about which little is known. Although cure rates have dramatically increased in pediatric cancer, palliative care and hospice are an integral part of caring for the patients who do not survive. A better understanding of why parents and patients choose hospice can help improve the care of pediatric oncology patients at the end of life.

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.  

The treatments used to cure pediatric cancers can cause infertility. Banking sperm at diagnosis is the gold standard for preserving fertility for boys who have reached puberty, but is not an option for younger boys who do not yet have mature sperm in their testicles. The prepubertal testicle does contain a small number of stem (parent) cells that will eventually become mature sperm, so one new idea is the use of testicular tissue frozen at diagnosis, then later thawed with the parent cells reimplanted into the testis to mature or matured outside the body and then used with assistive reproductive techniques. This consortium is collecting testicular tissue samples to increase the amount of tissue available for research, in the hope of providing an option for fertility preservation to patients who currently have no options at all.  Funds administered by the Children's Hospital of Philadelphia.

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.

To identify new therapeutic approaches in high-risk childhood acute lymphoblastic leukemia (ALL), this consortium of investigators has performed detailed analysis of genetic mutations in high-risk ALL. Pilot studies have identified over 40 new mutations and chromosomal rearrangements, several of which may be targeted by new treatment approaches. Following this, the group is performing mutation testing of larger numbers of childhood ALL samples to learn the nature and frequency of these mutations. This is the most comprehensive survey of genetic changes in childhood leukemia to date, and is likely to provide crucial new insights into the biology of this disease. Funds administered by the University of California, San Francisco.

This study focuses on neuroblastoma, a childhood cancer in which amplification of the MYCN proto-oncogene is associated with older age, rapid tumor progression, and the worst outcome. High-level expression of MYCN is thought to cause an aggressive behavior of the tumors. Researchers have identified several compounds that can rapidly destabilize the MYCN protein (within a few hours) in neuroblastoma cells, suppressing tumor growth. This research is to better understand the biological functions of MYCN and pVHL and their relationship in neuroblastoma, laying a foundation for therapeutic strategies against the disease.

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.

Neuroblastoma is one of the most common cancers of childhood, accounting for 15% of pediatric cancer deaths. ALK kinase is a protein involved in signal transduction pathway leading to cell proliferation. Amplification of the MYCN gene is found in 20% of neuroblastoma and results in an especially aggressive cancer. This project is to help understand how these two genetic alterations result in the development and progression of neuroblastoma. The long-term goal is to better understand the biological mechanisms that give rise to neuroblastoma and to develop novel therapeutic approaches.