Grants Search Results

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 an undergraduate student to complete work in pediatric oncology research for the summer. DIPG's are the worst type of brain cancer children can get; there is no cure. This project will try a new approach to change that. Using large publicly available datasets from large experiments, 4 drugs have been identified that theoretically can slow down the growth of DIPG tumors. Researchers will test these four drugs against several DIPG models generated from patients. If results are positive, this could lead to new treatments for this deadly disease.

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 an undergraduate student to complete work in pediatric oncology research for the summer. High risk neuroblastoma remains a challenge to cure with only 50% survival, despite multi-modality treatment. Natural killer (NK) cells have been previously shown to have activity versus neuroblastoma but have not been consistently successful in clinical trials. In similar fashion to how people receive flu shots, this project will treat bone marrow transplant recipients with 3 doses of a vaccine, with or without anti-PD1 therapy to stimulate T and NK cells, to introduce their immune system to what neuroblastoma looks like, so in the event this tumor tries to grow, the immune system will stop it and kill it before making the patient sick. 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.

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.

Malignant brain tumors are the most common cause of cancer-related death in children. The current standard of care treatment is often associated with lifelong cognitive and motor deficits and is almost inevitably followed by disease recurrence. Therapies that specifically and efficiently target tumor cells and minimize toxicity to normal cells are thus critical to the next generation of interventions that promise improved clinical outcomes for children affected by these deadly diseases. Capitalizing on our current knowledge of tumor metabolism and how metabolic pathways affect immune response, Dr. Deleyrolle is testing an innovative therapeutic modality based on reprograming the metabolic qualities of anti-tumor immune cells to enhance immunotherapy for childhood cancer. Successful completion of this project will demonstrate that immunometabolism represents a viable and critical target for the development of new cancer therapies to treat pediatric cancers, especially brain tumors. Dr. Deleyrolle is the recipient of the Pray for Dominic St. Baldrick's Research Grant. This grant is funded by the Pray for Dominic Hero Fund which was established in honor of an amazing boy who had so much joy and compassion for others even in a difficult battle with a rare and aggressive cancer. This fund carries on Dominic's legacy of joy and hope by funding research for high grade gliomas such as glioblastoma and DIPG for which there is no cure. This grant is named for the Pray for Dominic Hero Fund. The fund was established in honor of Dominic Liples who lived with joy. He is remembered for compassion and determination while he faced his own difficult battle with a rare and aggressive brain cancer. The Pray for Dominic fund carries on Dominic's legacy of joy and hope by funding research for high-grade gliomas.

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.

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.

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.

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.

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.

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.

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.

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.

There is a type of leukemia which occurs mainly in infants, but also in children who have previously received chemotherapy for an unrelated cancer. This type of leukemia is extremely difficult to treat and often comes back despite chemotherapy. We have evidence that this leukemia relies on a protein called MBNL1. By disrupting MBNL1, leukemia cells cannot produce specific proteins they need to grow. As the Julia's Legacy of Hope St. Baldrick's Scholar, Dr. Lee, as proof of concept, has shown that MBNL1 can be blocked by a chemical inhibitor. By using computer models, testing large libraries of drug-like chemicals, and applying special chemistry techniques to improve how effective a drug is, Dr. Lee is looking for a way to block MBNL1 with a drug that can be used in humans. This will lead to a new therapy for this class of leukemias. A portion of this grant is named for Julia's Legacy of Hope, a 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.

Based on progress to date, Dr. Stanton was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. Rhabdomyosarcoma (RMS) is a highly aggressive and lethal pediatric cancer affecting children and adolescents and arises in the soft tissue and skeletal muscle of the extremities, head and neck, and reproductive organs. From the clinical perspective, although patient outcomes have improved in general, nevertheless survival rates for some RMS tumors remains at less than 30%. One particularly aggressive subtype is alveolar RMS which is driven by the occurrence of chromosomal translocations resulting in the generation of chimeric or fusion proteins between the PAX3 or PAX7 and the FOXO1 genes. These are known as fusion-positive RMS (FP-RMS) and are associated with reduced relapse-free survival and generally poorer outcomes. But researchers still have limited understanding of how the "fusion" gene itself is driving the tumor, and no subtype-specific therapies exist. Dr. Stanton aims to determine how the fusion gene works with a protein complex known as BAF, to alter the epigenetic state of the cell to keep them dividing and stop the cell from differentiating into mature muscle tissue. His team is exploring the mechanism of how the BAF complex regulates the epigenetic state and memory of the FP-RMS. Furthermore, using small-molecule drugs and genetic depletion strategies (CRISPR) they will determine if FP-RMS tumors are dependent on the BAF complex for survival. Finally, they are working to identify potential novel therapies for patients with aggressive and lethal FP-RMS, to improve their outcome. The 2021 and 2022 portions of this grant is funded by and named for the Aiden's Army Fund. When he was 8 years old, Aiden Binkley was diagnosed with Stage IV rhabdomyosarcoma. He had a huge tumor in his pelvis and the cancer had metastasized to his lungs. But this bright, funny and courageous boy believed he got cancer so he could grow up to find a cure for it. Aiden’s story has inspired so many people and his vision to cure cancer is being carried on by Aiden’s Army through the funding of research. They will march until there is a cure! The 2020 and 2023 portions of this grant is funded by and named for by Berry Strong, a St. Baldrick’s Hero Fund, established in honor of Caroline Berry. Diagnosed with alveolar rhabdomyosarcoma when she was 14, Caroline endured a two-year battle with courage and determination. Throughout treatments of radiation and chemotherapy and undergoing six surgeries, Caroline was a beacon of hope, unselfishly raising awareness and funding for research so no child would have to endure what she did. After a brief remission, scans revealed Caroline had relapsed and she passed away on Thanksgiving in 2018. Caroline is remembered as a bright light, creative, intelligent, funny and feisty who was always eager to share a smile with others. She continues to be an inspiration through the Berry Strong Hero Fund which will continue her legacy and her passion to raise awareness and fund the most promising childhood cancer research.

Leukemias are the most common cancer of childhood, and most often arise from cells of the B lymphocyte lineage (B cell precursor ALL, or B-ALL). While the prognosis for patients with standard-risk disease is good, the treatment of patients with relapsed or refractory B-ALL is difficult and thus new therapies are needed. Dr. Schuettpelz is studying the role of a cell-surface protein called CD53 in the regulation of malignant B cells. CD53 is more highly expressed on leukemia cells than on normal B cells, and has previously been shown to promote the survival of malignant cells. Using a model of B-ALL as well as human leukemia cells, she will test the effects of CD53 loss and gain on disease development and cell survival. Ultimately, she hopes that CD53 may be targeted therapeutically to treat patients with B-ALL.

Childhood leukemia patients diagnosed with MLL rearranged leukemia (MLL-r) have a particularly poor outcome. MLL-r cells are dividing endlessly, due to the constant growth signal sent by a protein located on the cell surface called FLT3. FLT3 signals can be regulated by chemically modifying the protein in a variety of ways. Dr. Li is exploring a novel way to regulate FLT3 by studying how the activity of FLT3 is regulated by PRMT1 mediated methylation, and evaluating whether a PRMT1 inhibitor in combination with the traditional FLT3 inhibitor could completely "turn off" survival signal of MLL-r leukemia.

Outcomes for children with acute lymphoblastic leukemia (ALL), the most common pediatric cancer, are dependent on age, biological subtype, and early response to therapy. Survival for certain subgroups have improved by intensifying therapy. Patients with persistent leukemia after the first month of therapy have an increased risk of future relapse, regardless of underlying leukemia subtype or treatment protocol. Therefore, patients with even low levels of persistent leukemia receive intensified therapy to induce complete molecular remission prior to stem cell transplant, making therapeutic targeting of low level residual leukemia important in the frontline setting. However, the biological features of this minimal residual disease have not been assessed and therefore precision approaches are currently out of reach. Understanding the biology of residual leukemia has critical implications for ongoing therapy. Vulnerabilities specific to leukemia cells that have survived during the early phases can be an avenue for future clinical trials for this population of patients. The biology of these rare leukemia cells may also be a window into the broader dynamics of ALL eradication. Even in cases with great responses to induction therapy with no detectable disease, patients require years of therapy to reduce the risk of relapse, demonstrating the residual leukemia cells are present. Such undetectable residual leukemia likely has similar biology to low level residual leukemia. Dr. Alexander is combining proven clinical tools that carry rich prognostic information, with flow cytometry approaches to isolate rare leukemia cells, and to utilize novel genomic tools including single cell analysis to describe the biology of residual leukemia.