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Diffuse midline gliomas (DMGs) are aggressive brain tumors in children that are almost uniformly fatal. Curative surgery is not possible, radiation therapy provides only temporary relief, and chemotherapies have proven wholly ineffective. New, effective therapies are desperately needed for children with these tumors, but decades of clinical trials have so far failed to improve outcomes. Researchers have now identified a specific mutation (H3K27M) that affects how DNA is organized and drives a majority of DMG tumors. This insight has yet to result in new treatment options, however, an emerging understanding suggests that other cellular changes are required for tumors to grow. As the Kids Shouldn't Have Cancer Foundation St. Baldrick's Fellow, Dr. Dahl and colleagues have identified a protein complex called the SEC that DMGs with the H3K27M mutation are dependent on for survival. This complex regulates how DMG cells read their genetic code. An existing class of drugs called CDK9 inhibitors are effective in blocking the activity of the SEC. Dr. Dahl is researching how the SEC acts to promote DMG cell growth and testing whether CDK9 inhibitors can be used to interrupt this process. If successful, this research will provide the rationale for the design of future clinical trials using CDK9 inhibition as a new way of treating this intractable disease.

The Kids Shouldn’t Have Cancer Foundation, a St. Baldrick's partner, was founded after Jon and Kimberly Wade lost their son, Jonny and twin to brother, Jacky to medulloblastoma. He endured countless surgeries and procedures, pain and fatigue yet maintained unshakable faith and grace through it all. As a result, he told his mother, “I don’t want any other kid to have cancer.” Their mission is to honor Jonny’s wish by conquering pediatric brain cancer through research and political action with an emphasis on responsible spending.

More frequently than previously recognized, children with leukemia have inherited mutations that make them likely to develop these cancers. These inherited syndromes are called leukemia predisposition syndromes and manifest with abnormalities in the bone marrow or leukemia. Recent studies have shown that these syndromes may account for over 10% of pediatric and young adult leukemia and the mutations in these patients may differ from adults with similar disease. Once leukemia develops in such patients, survival rates are drastically reduced, so many patients undergo painful and stressful annual bone marrow exams to monitor for leukemia. Major barriers to improving outcomes for these patients include: lack of markers for risk stratification, limited understanding of why these mutations lead to cancer and lack of understanding of why these patients have leukemia that is harder to treat. To better understand how disease-causing mutations arise in pediatric patients, Dr. Kennedy is analyzing genetic sequences from patients with a predisposition syndrome. These studies may be able to be performed on peripheral blood, sparing children bone marrow biopsies. Ultimately, she hopes that these studies will identify novel ways to monitor and treat pediatric and young adult patients at high risk for leukemia.

Clinical trials have been essential to the great progress that has been made toward curing childhood cancer. New personalized therapies in current clinical trials promise to be more effective and less toxic than drugs in the past. But, to truly understand what a child finds most bothersome and provide the best quality of life possible, we need to ask the child directly. No one has done this for children receiving personalized therapies for cancer that has returned or not responded to chemotherapy, a group where quality of life is especially important. To answer this question, a team from Seattle Childrens Hospital/University of Washington and Boston Childrens Hospital/Dana Farber Research Institute designed this study. Dr. Steineck and colleagues are using surveys, especially made for children, to learn what children feel when they are treated on a clinical trial and what bothers them the most. This will help doctors find better ways to recognize and treat these symptoms, alleviate suffering, and improve how children view their quality of life. Knowing this is important for families to understand what their child may experience with treatments used on todays clinical trials and guide them in their very important, but difficult decision about the care their child receives.

This grant is funded by and named for Friends for Hope, a St. Baldrick's Hero Fund created to honor Morgan Loudon and celebrate her strength and determination as a cancer survivor. Morgan was 9 years old when she was diagnosed with a rare rhabdoid tumor and today she has no evidence of disease. With this fund, the Loudon family hopes to rally family and friends to “battle on” in the search for cures and better treatments.
This grant was awarded at Seattle Children's and transferred to Medical College of Wisconsin.

There is a great need for new therapies for pediatric acute myeloid leukemia (AML), both to improve cure rates and to decrease toxicities of the current standard of care, which includes intense chemotherapy and often bone marrow transplant. Chimeric antigen receptor (CAR) T cells represent one such opportunity to improve care for these patients, especially given the success of CAR T cells in patients with other types of leukemia and lymphoma. Dr. Richards and colleagues have identified a protein called CD93 as a potential target on AML cells, and have generated CAR T cells that are specific for this target. Preliminary data show that these cells meet criteria for an effective CAR and show promise for potential translation to patients in the future. Dr. Richards is focusing on extending the initial testing of these CAR T cells to determine efficacy in treating leukemia in pre-clinical models and evaluating for possible toxicities as we consider the possibility of moving this therapy toward clinical trials in the future.

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.