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Neuroblastoma is a common solid tumor in children, accounting for 1 in 10 new cancer diagnoses. Approximately half of the children with the high-risk form of the disease will die, and the survivors will bear a lifelong burden from the intensity of therapy. We are desperately in need of novel treatment approaches. The most aggressive neuroblastomas have extra copies of a gene called MYCN, which causes neuroblastoma cells to have different metabolism from normal cells. As the Mighty Micah's Mission Fund St. Baldrick's Fellow, Dr. Maxwell is investigating the abnormal metabolism of neuroblastoma in order to uncover new potential therapies. He has found that the amino acid, asparagine, is critical to the growth and survival of neuroblastoma, and has identified two medications (called DON and asparaginase) that, when combined, reduce the levels of this critical nutrient and effectively kill the most aggressive neuroblastomas. This work could serve as the basis for new clinical trials with this drug combination in children with neuroblastoma. Dr. Maxwell aims to exploit neuroblastoma's metabolic Achilles' heel in order to improve outcomes for children who suffer from this devastating disease. This approach holds great promise for future targeted therapies to treat not only neuroblastoma, but many other cancers that rely on abnormal metabolism.

This grant is named for Mighty Micah's Mission Fund, a St. Baldrick's Hero Fund. Diagnosed when he was 15 months old with high risk neuroblastoma, Micah was in treatment for nearly 7 years and survived two relapses. Thanks to research supported by St. Baldrick’s and the development of a new drug that is less toxic and more effective, Micah has no evidence of disease today. He has been named a 2020 Ambassador for St. Baldrick’s and as a science fan who hopes to become a doctor one day, Micah is grateful to the researchers who strive to find cures: “Those medicines save kids’ lives and one of them saved mine.” This fund honors Micah’s cancer journey and supports neuroblastoma research to find better treatments and cures for kids with this disease.

Children and adolescents everywhere in the world get cancer and both the type of cancer, and perhaps more importantly, where they live in the world, factor into whether they live or die. This is due to major disparities between countries in access to optimal treatment, early abandonment of therapy despite the potential for cure, and availability of quality supportive care. Acute lymphoblastic leukemia (ALL), the most common childhood cancer, is mostly curable in countries with strong health systems, like the United States. However, we do not know the exact number of children and adolescents who develop and die from ALL worldwide, because many countries with limited resources also lack quality health registration systems. Identification of context-appropriate strategies to prevent future deaths in children with ALL are necessary, and when combined with improved burden estimates, can guide policy decisions more effectively. Knowing that the majority of countries in the world have limited resources, this project will determine what the best interventions are to improve outcomes for children and adolescents with ALL now, while testing ways to improve estimates of the number of children with ALL who are currently not correctly diagnosed or do not reach healthcare. Awarded at St. Jude Children's Research Hospital and transferred to University of Washington.

Eight out of ten children with cancer will be cured and will become long-term survivors. However, children with cancer experience serious side-effects during, and even after, finishing treatment that negatively affect their well-being. There is also variation and unpredictability in who will experience these side-effects. Additionally, despite the best treatments, some children are not cured and ultimately lose their fight against cancer. Dr. Wadhwa is examining the role played by body composition (fat and muscle) of children with cancer on side-effects and cure rates. The dose of chemotherapy has been based on height and weight. Dr. Wadhwa and colleagues believe that body composition plays an important role in how the chemotherapy is distributed in the various compartments of the body. They are using routinely performed CT scans to determine body composition and plan to identify a method to personalize the chemotherapy dose for each child and minimize serious side-effects but at the same time, maximize cure rates.

This grant funds a student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. This student is working under the supervision of a senior fellow to validate newly discovered immunotherapy targets in AML. The student is using molecular biology techniques to test top 20-30 candidate genes for expression in childhood AML. Validated genes will be used for further immunotherapy development.

This grant funds two undergraduate students to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Project 1: The current treatment strategy for brainstem gliomas is radiotherapy alone, as neurosurgery is not practical due to nearby vital structures. These researchers hypothesize that the development of therapeutics to radiosensitize cancer cells will increase DNA damage, leading to enhanced tumor cell death and ultimately an improvement in patient survival. To investigate the mechanisms of radiosensitization in brainstem gliomas, the student is assisting in utilizing models lacking the DNA damage response protein, ATM, or molecular inhibitors of ATM. The focus will be to investigate how the spectrum of mutations in tumors affects radiosensitization in the absence of functional ATM. Project 2: Rhabdomyosarcoma (RMS) is the most common connective tissue cancer of childhood. The alveolar variant (ARMS) is particularly hard to cure. A common genetic error in ARMS is the mutant protein PAX3-FOXO1, which turns on cellular programs that tell ARMS cells to keep dividing. However, PAX3-FOXO1 is not a good drug target and it does not work alone – it physically interacts with other proteins that carry out its cancer-causing instructions. Recently a team of three labs including this one collaborated to identify such proteins. One of the top discoveries was a protein called CDK8. Not much is known about the job of CDK8 in ARMS, this student will help reveal new information about ARMS.

This grant funds a graduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. HPV vaccination is an important but underutilized tool to ensure the long-term health of childhood and adolescent cancer survivors. Survivors of childhood and adolescent cancers are at higher risk for HPV-related health risks, including HPV-related cancers, than the general population. Unfortunately, their rate of HPV vaccination is much lower than the general population. This study will explore communication strategies related to the HPV vaccine among survivors being seen for follow-up care in an oncology setting. Interviews will be conducted with survivors (ages 18-26) as well as parents of survivors to understand their concerns about and barriers to HPV vaccination and to create specific communication strategies for oncology providers to discuss the HPV vaccine with survivors.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Raman spectroscopy (RESpect) is an innovative tool that can be applied to biological specimens to obtain RESpect fingerprints of cancer tissue. RESpect signatures will be obtained from different childhood cancer tissues using the standard RESpect tool in the lab and compare them to the RESpect fingerprints that are obtained from a portable RESpect probe. Applying RESpect technology using a portable RESpect probe has the exciting potential that a portable probe could be used in the clinical setting to quickly assess whether a child might need further assessment to determine if a cancer is present. The St. Baldrick’s Foundation Summer Fellow is collaborating with physicians, engineers and scientists with the potential to make an important contribution on discovering a novel application of RESpect technology.

This grant funds a medical school student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. T-cell acute lymphoblastic leukemia is a deadly pediatric cancer that requires the use of highly toxic treatment. Doctors still do not know the mechanisms that lead to development of this type of leukemia. This award will train a medical student to perform experiments to identify novel targets for treatment and to help us understand the mechanisms that regulate activities of genes in T-cell leukemia.

This grant funds a medical school student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Diffuse large B-cell lymphoma (DLBCL) makes up 10-20% of pediatric non-Hodgkin lymphomas. Although its prognosis is improving, it requires up to six months of intensive chemotherapy. Abnormal lymphocytes in DLBCL have high energy demands, so if we could exhaust their energy source, we could arrest abnormal B cell proliferation. This project aims to develop novel, targeted therapy, by depleting energy reserve for B cells, in treating childhood blood cancers.

This grant funds a student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. B cell acute lymphoblastic leukemia is the most common pediatric cancer. The most deadly subtype of this disease has high levels of the CRLF2 protein. Leukemia cells of this type can be killed when treated with high doses of a naturally occurring molecule in the body. This molecule shuts down cancer causing signals produced by CRLF2. This award will provide resources for a medical student to perform experiments to help us understand the mechanisms that this molecule uses to exerts its anti-leukemia effects so that it can be developed as a new treatment for high-risk leukemia.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric cancer with 10% overall survival 2 years from diagnosis. K27M mutations within histone H3 are the hallmark of DIPG. Panobinostat, a drug targeting epigenetic changes, has shown some promise in DIPG by multiple groups. These researchers' genomic analysis of DIPG cell lines shows that the cancer may be driven by LIN28. DFMO (a-difluoromethylornithine) decreases LIN28 protein levels in neuroblastoma and may be effective in treating DIPG. Therefore, the hypothesis is that co-treatment of DIPG with DFMO and panobinostat will result in increased cell death in DIPG and be an option for patients.

This grant funds a graduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Neuroblastoma (NB) is an early childhood cancer for which more effective therapies are urgently needed. Immunotherapy has been promising for blood cancers, but in solid tumors like NB, immune cells must compete with tumors for limited nutrients to sustain their function. In NB tumors, these researchers found a high frequency of a type of tumor-killing T cell with unique functional properties that may effectively shrink tumors and improve patient survival. The student is assisting in activating these cells in neuroblastoma tumor models and investigate their cellular properties, with the goal of providing a foundation for more informed immunotherapy of NB and other solid tumors.

This grant funds two students to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Project 1: There is tremendous excitement surrounding immune checkpoint inhibitor therapies. However, debate continues regarding whether pediatric cancers can benefit from such approaches, as immune checkpoint expressions are often variable and low on pediatric tumors. The student will investigate molecular signaling crosstalk, thereby providing new molecular targets for immune checkpoint blockade for childhood cancers. Project 2: Osteosarcoma (OS) is the most common malignant primary bone cancer in the pediatric and adolescent population, with about 20% of these patients presenting with pulmonary metastasis at diagnosis, while about 30% develop lung metastasis (Lung OS) after therapy initiation, accounting for most of the OS-related mortality. The SBF summer fellow will investigate the how integrin signaling associated with this.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. In this summer project in the Ruggero lab, the student will learn and employ cutting edge biological techniques to identify proteins that drive medulloblastoma, focusing on specific proteins whose abundance is regulated by MYC genes.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. More than 80% of children with cancer before the age of 20 years will survive beyond 5 years from diagnosis. The exposure to chemotherapy causes both short-term as well as long-term health issues in these individuals. Exercise interventions in adults with cancer demonstrate significant benefits in health, however, there are no studies examining the effects in pediatric, adolescent and young adult cancer survivors. This study will determine if a one-on-one supervised exercise program or exercise intervention personalized for adolescent and young adult (AYA) cancer survivors (15 and 29 years age) will significantly improve chemotherapy-induced health issues.

This grant funds a medical school student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Brain tumors are the second most common childhood malignancy. Magnetic resonance imaging (MRI) is the gold-standard for detecting brain tumors. This project aims to establish novel physiological MRI protocols for non-invasive characterization of the immune and inflammatory milieu of pediatric brain tumors following radiation and immunotherapies in models.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Ewing Sarcoma (ES) is an aggressive pediatric cancer. The disease has the worst prognosis when metastases are present, however mechanisms promoting its spread are not clear. These researchers have discovered a new mode of ES spread – migration along nerves. The data indicates that this process is stimulated by a protein released from these nerves – neuropeptide Y (NPY). The student is helping to identify molecules present in ES that recognize NPY and promote their invasion along the nerves, as well as test strategies preventing this effect. If successful, this study may impact ES patients by preventing tumor dissemination.

This grant funds a medical school student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Neuroblastoma is an often-deadly malignant childhood cancer. Research in the DeClerck lab has shown that non-cancerous stromal support cells in neuroblastoma tumors play an important role in the malignant behavior of the tumor by communicating between each other. A newly-recognized method for cell communication is via little vesicles called exosomes. These are released from one cell type and are captured by other cell types in the tumor and can affect tumor malignancy and resistance to therapy. In this project, the student is examining communication through such exosome vesicles between stromal cells and neuroblastoma tumor cells.

Unlike many other pediatric cancers, osteosarcoma has many abnormalities found on genetic analysis of the tumor itself. Dr. Sweet Cordero and colleagues hypothesize that some of these abnormalities could be used to predict what treatment might work best for each specific osteosarcoma patient. For example, many osteosarcomas have genetic alterations that block their ability to "repair" their DNA using specific pathways. One of these defective pathways is called the "homologous repair" pathway and another is called the "alternative lengthening of chromosomes" pathway. The inability of osteosarcoma tumors to repair their DNA using these pathways may make them susceptible to specific drugs. However, it is very likely that these drugs will need to be used in combination and not alone. A key need to advance osteosarcoma patient care is to define and use appropriate model systems to test drugs before using them in patients. This project is combining both preclinical studies in PDX models and a clinical trial to develop new ways to treat osteosarcoma patients with the goal being to improve survival for patients with relapsed and metastatic disease.

This multi-year grant is named for and funded by the Battle Osteosarcoma Hero Fund inspired by and established in honor of Charlotte, Dylan, Tyler and all OsteoWarriors. Led by parents, its mission is to raise funds for promising osteosarcoma precision oncology research to improve treatment options and outcomes for kids battling osteosarcoma.

Therapeutic access to pediatric solid tumors, especially in the context of metastatic disease, remains a tremendous challenge. Dr Daugaard and his team are developing new ways of targeting pediatric solid tumors by exploiting distinct changes to proteins expressed on the surface of tumor cells and in the tumor microenvironment. The St. Baldrick's Robert J. Arceci Innovation Award is given in honor of the late Dr. Robert Arceci. A pioneer in the field, this award reflects Dr. Arceci's values including creativity, collaboration, and commitment to early- to mid-career scientists.