Grants Search Results

Ewing sarcoma is an aggressive bone and soft tissue cancer that primarily affects children and adolescents. Patients often suffer severe side-effects from treatment and there are no second-line therapies for relapsed tumors. It is critical that we develop new and less toxic treatments for this cancer. Ewing Sarcoma is caused by a rearrangement of DNA that fuses pieces of two different proteins together to form a new protein. This new protein, called EWS-FLI1, can turn on genes that should not be on, leading to the transformation of the cell into an Ewing Sarcoma tumor. This fusion protein has features that make it very difficult to study, it sticks to itself and does not have a structure, a good analogy is that it behaves like a piece of cooked spaghetti. As the Shohet Family Fund for Ewing Sarcoma Research St. Baldrick's Scholar, Dr. Libich is utilizing his background in working with similar proteins that do not have structure. He is using NMR (nuclear magnetic resonance) which works just like MRI, to peer into the protein to understand exactly how it functions. This information is critical for designing molecules (drugs) that will be able to only affect the function of EWS-FLI1 and thus open new ways of attacking Ewing's sarcoma.

This grant is funded by and named for the Shohet Family Fund for Ewing Sarcoma Research. In his freshman year of college, Noah was diagnosed with Ewing sarcoma. He endured many months of chemotherapy and had limb salvage surgery. Able to return to school, Noah had no evidence of disease for 2½ years until April 2018 when routine scans revealed he had relapsed. He passed away in May 2021 at the age of 25. Noah and his family were always passionate about the need for curative treatments for diseases of the AYA population. The Shohet family intends to raise funds for this Hero Fund in Noah's memory to find cures for Ewing sarcoma and to carry on his legacy of possibilities and hope.

Survivors of cancer have a higher risk of health problems because of the severity of the chemotherapy and radiation treatments they received. As survivors of childhood cancer age, they increasingly succumb to the "late effects" of their cancer treatment (such as second cancers and heart and lung disease). After 10-15 years, these late effects become the leading causes of death in this population. Adolescents and young adults (AYAs, aged 15-39) are a subgroup of cancer patients that are defined as high risk because they: more commonly suffer from toxicities and side effects of their cancer treatment; have unique barriers to accessing health care; and suffer specific psychosocial concerns because of their life stage transitioning into adulthood. To date, little research has been done on the factors that influence long-term health outcomes in the population of survivors of AYA cancer. Dr. Moke is working to explore how cancer and its treatments affect health later on in life in survivors of AYA cancer, identify the causes of death in this population, and determine what factors and cancer treatments are associated with these specific life threatening health problems. This study will provide the baseline data needed to design ways to decrease the severity of and death from these late effects, and thus be an important step in promoting long and healthy lives in survivors of AYA cancer.

Based on progress to date, Dr. Johnston was awarded a new grant in 2022 to fund an additional year of this Scholar grant. Hospice (home-based end of life care focusing on pain control and emotional support) leads to better quality of life for the dying person and easier grief for families when an adult dies of cancer. We do not know if the same is true in children. We do not know rates of hospice use in children dying of cancer, what inequalities exist, nor how families perceive hospice, especially in minorities. Dr. Johnston aims to better understand US pediatric hospice use with a focus on minorities. Her team will determine rates of and inequities in hospice use in children dying of cancer nationally and then interview families that had a child die of cancer and pediatric oncology and hospice teams to determine if the inequities are in line with child and family preferences. Early palliative care in adults leads to better quality of life and more hospice and home death. It is unknown if the same is true in children with cancer. Dr. Johnston and colleagues will offer early palliative care to children with brain tumors to determine if early palliative care is acceptable to families and providers and if a randomized control trial would be possible. After this project, she will be able to use information and skills gained to design a trial aimed at improving hospice access for those that desire hospice that builds on the lessons learned in this study. Researchers will then better understand hospice in children with cancer, necessary to ensure all children dying of cancer have high quality end of life care.

Based on progress to date, Dr. Velasquez was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. Childhood acute myeloid leukemia (AML) is a blood cancer that is very difficult to treat in children and adolescents. T cells are one component of the patient's own immune system that helps defend against infections. New cancer treatments use modified T-cells that can ‘see' and kill cells that have CD123, a molecule present on AML, and have shown promising results in studies in the laboratory. Dr. Velasquez is testing if these specific T-cells are safe and can kill leukemia cells in children that have AML that came back after initial treatment. She also wants to see what happens to these T-cells after they have been given to the patient and how it affects the tumor. This information from the treated patients and the study of their T-cells and tumor cells will be useful in finding a cure for AML.

Osteosarcoma is a cancer of bone that happens in young people. Dr. Davis and colleagues are trying to find ways to help the immune system fight off tumor cells, which may help us find a cure. They are examining all of the different type of immune cells in over 100 osteosarcoma tumor samples to identify how patterns in the cells match with other characteristics, such as how well a patient does with standard osteosarcoma treatment. They are also looking at biopsies from patients before and after immune therapy and will try to boost responses to immune therapy with a targeted drug. By understanding the way the immune system "sees" (or doesn't see) osteosarcoma, they will be able to predict which patients will benefit from different types of immune therapy and who will need other drugs added to their treatment regimen.

A portion of this grant is generously supported by the Sweet Caroline Fund, a St. Baldrick's Hero Fund, created to honor the memory of Caroline Richards who was diagnosed in 2014 with osteosarcoma in her right arm when she was 11 years old. She persevered through rigorous treatments with a giving spirit and a contagious smile, always thinking of how to make others happy or laugh. Caroline sadly lost her battle a year later but this fund pays tribute to her compassion for others by supporting osteosarcoma research to help kids with cancer.

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. Millions of cells are formed every day in the developing brain of children. Medulloblastoma, a pediatric tumor, occurs when the proliferation of cells in the cerebellum (a lower part of the brain) becomes uncontrolled. The Notch pathway is a key mechanism that governs cell proliferation in many biological contexts. Aberrant up-regulation of Notch signals is associated with medulloblastoma. Re-gaining control of Notch could help cure medulloblastoma patients. The goal of the Rual laboratory is to better understand the molecular mechanisms that control Notch signals in brain cells and, thus, to define novel therapeutic targets for the benefit of medulloblastoma patients. This lab recently identified the L3MBTL3 gene as a new modulator of Notch signals. Importantly, previous studies have shown that the L3MBTL3 genes is deleted in medulloblastoma patients. These researchers hypothesize that the L3MBTL3 deletions observed in medulloblastoma patients result in the aberrant regulation of Notch signals, thus supporting tumorigenesis. In this project, the student is helping to test this hypothesis by studying the extent to which inhibiting L3MBTL3 modulate medulloblastoma tumor progression in models of medulloblastoma.

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. Sarcoma is a type of cancer that arises in the bones, muscle or fat. In children, sarcoma continues to pose a formidable clinical challenge because it is frequently resistant to current treatments (chemotherapy and radiation). This student is helping to test the theory that a cancer-causing gene called ROS1 drives the aggressive growth of some sarcoma tumors. There are already FDA approved ROS1 drugs, and these are effective in adults with ROS1-driven lung cancer. Our overall goal is to validate known cancer causing genes, and repurpose safe drugs so that fewer children succumb to sarcoma, and the survivors have excellent long-term quality of life.

Lymphoma and leukemia are cancers that often strike children. Some types of these cancers cannot grow or survive without a protein called MALT1. As the Do It For Dominic Fund St. Baldrick's Fellow, Dr. Maurer found that, in some lymphoma cells, when the level of another protein called GRK2 was lowered, it led to more action of the MALT1, and more cancer growth. So, she thinks that GRK2 might be working to stop lymphoma tumors by blocking MALT1. She is working to find out two things: Does the level of GRK2 also affect the growth of leukemia? And how exactly does GRK2 interact with MALT1 to block its tumor-growing action? Understanding this interaction will help to design new treatments that work by blocking the MALT1 and stopping the growth of lymphoma cells, and perhaps leukemia cells too, so that children can be cured.

This grant is named for the Do It for Dominic Fund which honors the memory of Dominic Cairo who battled non-Hodgkins lymphoma and was a hero to his school and community. His family and friends continue to raise funds and support research in the hopes that no child has to go through what Dominic endured.

Osteosarcoma (OS) is the most common malignant bone tumor in children, but only five chemotherapy drugs have been shown to be beneficial, and overall survival remains poor (60%). There are no effective standard-of-care therapies for patients who relapse. Identifying new treatment strategies in OS is of paramount importance. Prior studies evaluating the genetic code of OS tumors show significant genetic heterogeneity among patients and have not uncovered recurrent changes that can be successfully targeted. Dr. Pavisic is using computational algorithms established by the Califano laboratory to identify universal tumor dependencies known as master regulator (MR) proteins from the messages expressed by the tumor’s genetic code to make proteins (RNA). Using information from drug studies done in OS cells, she is prioritizing drugs by their ability to reverse the activity of a tumor’s most aberrantly active MR proteins. MR proteins integrate the effects of many genetic alterations and are critical to tumor cell survival, thus represent novel tumor biomarkers and drug targets. Dr. Pavisic hypothesizes that MR analysis in OS will lead to biologically-relevant patient classification and risk stratification, and prioritize new drugs for immediate testing in laboratory models of OS and in clinical trials to improve outcomes for children with OS.

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.