Grants Search Results

Over the past 10 years, we have made great strides in the diagnosis of Medulloblastoma, the most common malignant brain tumor of childhood. These advances have come from widely collaborative efforts to perform DNA sequencing on tumor specimens. This effort led to the identification of major subtypes of Medulloblastoma and a recognition that these subtypes are associated with differences in response to standard treatments and survival. Lagging behind, has been an understanding of the molecular mechanisms that drive relapse of Medulloblastoma. This occurs in 30-40% of Medulloblastoma patients and as yet, there are no curative options. As the recipient of the Thumbs Up Fund to Honor Brett Haubrich St. Baldrick's Research Grant, Dr. Rubin and his team members are proposing a novel clinical trial to address this pressing unmet need. Their trial, brings together what has been learned from sequencing Medulloblastoma and the recently developed ability to test the sensitivity of an individual patient's Medulloblastoma cells to hundreds of drugs simultaneously. The long-term goal is to use the combination of drug testing and DNA sequencing to design personalized treatments for relapsed Medulloblastoma patients. Success in this effort would not only provide new treatments for relapsed Medulloblastoma, but would also provide a new paradigm for personalized approaches to the treatment of all pediatric brain tumors. A portion of this grant is funded by and named in honor of The Thumbs Up Fund to Honor Brett Haubrich, a St. Baldrick's Hero Fund. Brett is remembered for his kindness, his joy in making others happy and his faith even through his 3 ½ year battle with anaplastic astrocytoma, a difficult to cure brain cancer. Brett was diagnosed at the age of 11 and endured treatments and laser surgery which impacted his motor and speech functions. Yet he was always positive, often giving his signature “thumbs up” as a symbol of hope. In his honor, Team Brett began participating in St. Baldrick’s head shaving events in 2015 and each year, raised over $10,000. This Hero Fund hopes to raise funds for childhood cancer research for brain tumors like Brett’s so other families would have more options for cures.

Alveolar rhabdomyosarcoma is one of the most aggressive and difficult to treat tumors in children. If not caught early, metastatic disease has a dismal 5-year survival of less than 5%, even after the most intensive chemotherapy possible. Even in the rare circumstances when these children do well, the long-term side effects of the intensive chemotherapy are debilitating. We can, and must, do better. We have known for some time that the cause of alveolar rhabdomyosarcoma in 60% of the most aggressive cases is a specific genetic abnormality. This genetic mistake creates a new gene, and Dr. Hiebert will determine how this new gene causes cancer and determine what would happen to these sarcoma cells if we had a drug specific for this new gene. To do this, he has engineered alveolar sarcoma cells grown in the lab so that this cancer gene can be quickly turned off by an existing drug. This allows, for the first time, the treatment of these sarcoma cells with a specific drug to define all of the events that occur in the first few minutes to several days of drug treatment to establish that inhibition of this new cancer gene is a viable therapeutic strategy. This grant is generously supported by Rachael Chaffin’s Research Fund, a Hero Fund created in memory of a young girl who loved life. Rachael loved people, animals and the outdoors. It was heartbreaking when she was diagnosed with Rhabdomyosarcoma in the summer of 2013 at the age of 11. With a positive attitude and determination, Rachael began her long battle with cancer. She truly believed she would beat cancer so she could go on to help others. In 2014, Rachael organized a team of family and friends called “Kicking Cancer with Ray Ray” to raise funds for St. Baldrick’s and they continue the tradition today. This Hero Fund honors Rachael’s passion to find a cure for kids’ cancer and carries on her legacy of increasing awareness of childhood cancer to find better treatment options and cures through research.

Precise understanding of the basic mechanisms by which childhood cancers develop is essential to design tailored and superior treatments for cancer patients. These treatments are expected to cure and avoid long-term complications in cancer survivors. In many instances, we turn to models to reproduce human cancers, but the success of this strategy depends on how accurately we can unravel the origin of the disease. This project is based on Dr. Dominguez-Sola and colleagues recent findings on the origins and cellular basis of Burkitt lymphoma, a most aggressive form of childhood lymphoma with little treatment alternatives. This project will use unprecedented models of this cancer type to expand our understanding of the mechanisms of disease and identify therapeutic strategies that are less toxic, more effective, and superior to those currently available in the clinic.

Acute lymphoblastic leukemia (ALL) is the most common cancer of children, and although treatment is considered largely successful, in many cases leukemic cells stop responding to chemotherapy and re-emerge. As a consequence, ALL relapse remains a leading cause of childhood cancer-related death. Dr. Aifantis will test the possibility that the bone marrow microenvironment surrounding the leukemia supports the growth of disease and protects leukemia cells from chemotherapy. Together with colleagues he generated the first map of the ALL immune cell microenvironment allowing identification of novel players within the remodeled leukemic bone marrow that promote leukemia survival. They found that high levels of a specific cell type, known as non-classical monocytes, in ALL patient blood and bone marrow correlates with inferior patient survival. They demonstrated that depletion of leukemia-supporting monocytes enhances killing of leukemic cells with specific ALL therapies. In this project Dr. Aifantis will investigate the processes giving rise to monocytes capable of supporting leukemia survival. Further, he will use novel model systems to test whether targeting monocytes enhances responses to a range of existing ALL therapies as well as emerging approaches, such as Chimeric Antigen Receptor (CAR) T-cell therapy, that utilize a patient's own immune system to kill leukemic cells.

Cancer immunotherapy has demonstrated great potential for treating cancer. However, challenges such as 1) the lack of ideal targetable tumor antigens; 2) severe toxicity due to off-target interactions; and 3) tumor-mediated immunosuppression are limiting the success of immunotherapies to be broadly applicable. To potentially overcome these challenges, Dr. Wu and his colleagues have developed a programmable synthetic gene circuit platform that enables tumor-localized therapeutic payload production, for recruitment and activation of immune cells: Tumor Immuno-therapy by Gene-circuit Engineered Response (TIGER). This strategy makes use of the body's own immune system to kill tumor cells. Gene circuits (highly engineered DNA sequences that work together), delivered systemically, will be turned on by the presence of two cancer-specific signatures, therefore only be activated within cancer cells and not normal cells. Cancer cells will be forced by the activated gene circuits to produce immunomodulators. Dr. Wu has demonstrated that TIGER mediates robust therapeutic efficacy in vivo in solid tumors. They have also identified sensors that can distinguish high-grade stem-like glioma cells from non-stem-like glioma cells. To further accomplish clinical translation of this platform, several advances are required: 1) identification of tumor sensors that efficiently detect highly heterogeneous primary patient tumors, to optimize tumor-targeting efficiency and specificity; and 2) optimization of therapeutic output combinations for achieving maximal efficacy. This project will focus on advancing the above two aspects to facilitate clinical translation of TIGER to treat pediatric high-grade glioma and overcome existing barriers to effective immunotherapy. The first year of this grant is funded by and named for the Kai Slockers Pediatric Cancer Research Fund. Kai was diagnosed at 2½ with Atypical Teratoid Rhabdoid Tumor (ATRT), a rare and very aggressive brain cancer. Within two weeks of diagnosis, he passed away, a mere 3 months shy of his third birthday. When Kai took his last breath, the cloudy sky opened up with a bright ray of sun that streamed through the windows of his hospital room – the darkness of the disease was replaced with the light of hope and the peace of no more suffering. Whenever the sun is out, his family thinks of him, assured that his legacy of hope shines on. In his brief life, Kai shared his warmth, energy, goofy sense of humor, and caring heart with all those he met. This Hero Fund was created in his memory and will support research to help other kids with cancer have a better chance to fight and survive. It has a special focus on brain tumor research, specifically treatments that could minimize the harsh effects of brain tumor treatment. The Slockers family hopes to continue his legacy of light and hope through the funding of childhood cancer research. A portion of this grant is generously supported by the Derick the Defeater Fund, a St. Baldrick's Hero Fund. Derick was a hero in so many ways. Diagnosed with medulloblastoma at the age of six, he endured 2 years of treatment with determination and a positive spirit. He inspired friends and family with his smile and charisma, even advocating for other children fighting cancer and teaching everyone what it meant to be brave. Derick’s courage lives on in a comic book his friends created called “Derick the Defeater” about a superhero who fought evil villains that looked like cancer cells. This Hero Fund honors his legacy of helping others through the funding of childhood cancer research.

Based on progress to date, Dr. Reitman was awarded a new grant in 2022 to fund an additional year of this Fellow award. Brainstem gliomas are deadly brain tumors that affect children. The only effective treatment is radiation therapy, but despite this treatment all children with this disease eventually experience growth of the tumor and eventually death. As the Emily Beazley's Kures for Kids Fund St. Baldrick's Fellow, Dr. Reitman will test if treatments that enhance the efficacy of radiation therapy can improve survival in the laboratory. This could lead to new clinical trials aimed at helping children with brainstem gliomas to survive longer. This grant is funded by and named for Emily Beazley's Kures for Kids Fund. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma and battled through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle, inspiring a community to come together to show love and change lives. She had a dream of starting a foundation to fund research and named it “Kures for Kids”. Today, Emily's family and friends carry on her dream and her mission in her memory.

This grant funds a student to complete work in pediatric oncology research for the summer. There has been little success in curing high risk AML patients, with survival rates remaining at < 25%. This highlights our current reliance on highly intensive cytotoxic therapies and stem cell transplant, and their inadequacies. This project studies the combination of novel target discovery with state-of-the-art stem cell expansion technology. Protein science provides a unique opportunity to generate one of the most impactful therapeutic discoveries in childhood AML in the last 40 years, with minimal toxicity. The summer intern will assist in investigating the impact of drugs on cancer targets while minimizing toxicity toward healthy cells. Results will be used to help identify critical genes involved in cancer growth and disease resistance, and to leverage future work in drug development.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. This project will validate a drug for the medulloblastoma, a type of brain tumor, specifically tumors that spread from the original cerebellar location to the covering of the brain and spine (the meninges). This grant is named for the St. Baldrick's Foundation Staff whose generous gifts have helped fund this opportunity and may encourage students to choose childhood cancer research as a specialty.

This grant funds a student to complete work in pediatric oncology research for the summer. Osteosarcoma (OS) is the most common and highly lethal bone cancer affecting children and adolescent populations. New therapies are desperately needed for this highly aggressive disease, as outcome for metastatic OS has not improved over the past few decades despite the utilization of aggressive combination chemotherapy. The summer fellow will focus on testing a novel CA-IX small molecule inhibitor using syngeneic OS tumors in vitro and in vivo. Activities generated through this Summer Fellowship grant will lay the foundation for pre-clinical data for the use of CA-IX inhibitor in future clinical trials.

This grant funds two undergraduate students to complete work in pediatric oncology research for the summer. Tumors have extensive mutations in their DNA which play important roles in cancer development. Particular mutations that are frequently found in tumors are likely important for promoting cancer development. BubR1 is a protein that regulates the proper separation of DNA during cell division, and therefore plays an important role in suppressing cancer formation. A mutation in BubR1 (R249Q) is specifically observed in approximately 15% of pediatric cancers and is not found in adult cancers. Researchers will study this mutation and results may identify a unique mechanism of tumor development controlled by BubR1 specifically during developmental processes, uniquely promoting pediatric cancer. This project will provide an opportunity for these two students to spend the summer performing biomedical science research utilizing well-established and easy to learn techniques, to enhance their excitement in pediatric cancer research.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Ewing sarcoma is a cancer that primarily occurs in children, adolescents, and young adults. While we don't know why certain people get Ewing sarcoma, we do know that most patients have the same problem with genes in their cancer cell. Just as genes affect your eye color, the Ewing sarcoma cells have a special gene, EWS-FLI1, that keeps the cancer growing. EWS-FLI1 is critical for Ewing sarcoma cells to survive. If you turn off EWS-FLI1, Ewing sarcoma cells die. This project will study exactly how YK-4-279, a chemical in a new drug in clinical trials, affects key survival processes, called transcription and splicing, to enable design of optimized drugs. This grant is named for the St. Baldrick's Foundation Staff whose generous gifts have helped fund this opportunity and may encourage students to choose childhood cancer research as a specialty.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Diffuse intrinsic pontine glioma (DIPG) is a type of children's brain tumor that currently has no cure or effective therapeutic options. This proposal aims to understand whether the target drug of ONC201, ClpP, can be targeted using novel compounds representing new potential therapeutics in DIPG.

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: Neuroblastomas are an enigmatic cancer of childhood with subtypes that have extremely good or poor survival. Poor prognosis neuroblastomas contain normal immune cells that help tumors grow. Important questions are 1) what is the repertoire of immune cells in neuroblastomas at time of diagnosis, 2) how the interplay between normal and tumor cells changes when tumors recur. The Summer Fellow will analyze images of tumors at recurrence and compare to the diagnosis images. These findings will provide insights into the types of immune cells that cancer cells rely on and may allow identification of new targets of therapy. Project 2: Decline in brain function may happen after irradiation to the brain in children. It is hard to predict the extent and speed by which it happens. There is suggestion that more rapid injury happens in areas with iron deposition. Using a novel MRI method that allows chemical identification and quantification of iron in the brain, the Summer Fellow will characterize the imaging changes in white matter of the brain in children who have been treated with radiation for their brain tumors. This will allow to then correlate the changes with future outcome of their cognitive function.

This grant funds a medical student to complete work in pediatric oncology research for the summer. This year it is estimated that 800 children will be diagnosed with osteosarcoma (bone cancer). The lab has identified a gene (WNT5B) that is too high in a subset of osteosarcomas. By making a cell line that removes WNT5B, the lab will compare its growth to the original cells and target this gene in those cancers that have it to design a specific targeted therapy.

Ewing Sarcoma (EwS) is an aggressive bone and soft tissue tumor occurring in children and young adults. Approximately 25-30% of patients already have metastases at diagnosis and in spite of aggressive treatment, the survival for patients with metastatic disease remains dismal. EwS is considered an immune cold tumor that is largely resistant to conventional immunotherapy. Alternative treatment approaches are sorely needed, particularly in patients with metastatic disease. Dr. Sorensen and colleagues are using three novel strategies for targeting EwS tumors: 1) Inhibiting an EwS specific fusion protein that drives EwS tumor development. 2) Targeting a surface protein called IL1RAP. 3) Recruiting natural killer (NK) immune cells to EwS tumors and priming them to attack the tumor. This grant is the result of a generous anonymous donation to fund Ewing sarcoma research, specifically. It is in honor of a teenager fighting Ewing sarcoma, and is named the St. Baldrick's - Martha's Better Ewing Sarcoma Treatment (BEST) Grant for All.

Acute lymphoblastic leukemia (ALL) remains the most common cancer of children and young adults. Despite intensified treatments that achieved cure rates around 85%, there is a number of children who will relapse and succumb to therapy-resistant disease. One of the revolutions in the treatment of human cancer the last decade was immunotherapy, the ability of our own immune system to fight cancer. Unfortunately, despite its successes in a number of solid tumours, immunotherapy has not really impacted the treatment of leukemia, with the exception of CAR-T cell treatment of pediatric B-ALL. Indeed, some frequent types of pediatric ALL, and specifically T cell ALL (T-ALL) and its subtypes, have no immunotherapy treatment options. We believe that this is because we still don't understand how the cells of the immune system interact with the leukemia. Actually, researchers don't even know what type of immune cells are there available to fight the disease. Dr. Aifantis is applying a number of single cell techniques to create a map of the immune cells in the bone marrow of children with T-ALL. He is doing this at diagnosis of the disease, after treatment (remission) and when the children relapse. These studies will offer the first map of the immune system in pediatric ALL and will enable researchers to propose ways to activate the immune system to fight the tumour.

In the new era of personalized medicine, Ewing sarcoma still relies on decades-old chemotherapy options, where aggressive treatments are met with poor disease outcomes. Ewing sarcoma is a devastating disease that affects children and young adults age 5-16. Based on treatment outcome and patient qualities of life, Ewing sarcoma is in desperate need of research and development of new therapeutic options. One of the key observations of Ewing sarcoma made back in the 1930s is the accumulation of a large amount of glycogen. Glycogen is a sugar molecule that our body uses to store energy; only specific organs such as the liver and muscle are capable of producing glycogen. The ability of Ewing sarcoma tumors to store large amount of glycogen has been forgotten until now. Dr. Sun aims to understand the reason behind large glycogen accumulation in Ewing sarcoma and exploit the glycogen deposits as a possible drug target for the treatment of Ewing sarcoma. The successful completion of this project will bring new hope to this century-old disease and facilitate the development of the next generation of novel therapeutics specifically for Ewing sarcoma. A portion of this grant is funded by and named for Julia's Legacy of Hope, a St. Baldrick's Hero Fund that honors her positive and courageous spirit and carries out Julia's last wish: "no child should have to go through what I have experienced". Diagnosed at age 16 with Ewing sarcoma, Julia fought cancer and survived only to be stricken in college with acute myeloid leukemia, a secondary cancer as a result of treatment. Through this Hero Fund, her family hopes to raise awareness and funds for childhood cancer research especially for Adolescent and Young Adult (AYA) patients.

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. Ou was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. Due to the tumor and treatment damaging the developing brain, 60-80% of pediatric brain tumor survivors experience long-term neurocognitive impairment. There are two possible paths to improve outcomes: intervene the adverse brain development after treatment, or further optimize radiotherapy dose distribution in the brain before treatment. For the former, the question is to find at-risk patients to intervene after treatment. For the latter, the question is to find target brain regions, where changing radiation doses can potentially change outcomes. Both questions have been studied on the population-level, not on the individual level. This project aims to push our knowledge in these two fronts to the individual level. Dr. Ou is using data from 3 just finished clinical trials to find target patients and find target brain regions for radiation dose optimization. Compared to studies that consider one risk factor a time, Dr. Ou will consider a comprehensive set of risk factors to improve precision to the individual level. The results will allow him to design future larger-scale, multi-site retrospective replicative and eventually prospective clinical trials, to improve neurocognitive outcomes in this vulnerable population before and after treatment. This grant is generously supported by the Grace for Good Fund, established in honor of Grace Carey and celebrates her survivorship from medulloblastoma. Her cancer journey began in 2007 when she was diagnosed at age 5 with a treatment regime that entailed surgery, proton beam therapy and chemotherapy. While Grace handled it all with minor setbacks, she now faces the physical, emotional and cognitive challenges wrought by the very medications and procedures that saved her life. This fund was inspired by Grace’s desire to help other kids with cancer and supports research of brain tumors and the multitude of challenges facing survivors post treatment.

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.