Grants Search Results

This grant funds a student to complete work in pediatric oncology research for the summer. Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma in the United States, with approximately 400 new cases annually. Outcomes for high-risk RMS remain dismal, with three-year event-free survival rates as low as 20-30%. There is an urgent need for innovative therapeutic strategies that are more precise, have less toxicity and have significantly improved efficacy and survival benefits. A subset of RMS tumors have mutations in the RAS gene family, therefore, exploiting these mutations as therapeutic targets is an attractive and targeted therapeutic strategy. Dr. Ladanyi's research aims to test a recently developed RAS inhibitor (RMC-6236) in preclinical patient-derived disease models harboring mutations in RAS. This agent is in clinical trials for adult cancers with some RAS mutations. The St. Baldrick's Foundation Summer Fellow will help to generate the preclinical data necessary for a Phase 1 clinical trial testing RMC-6236 in children with RAS-driven RMS. This work is being completed under the mentorship of Dr. Marc Ladanyi.

This grant funds a student to complete work in pediatric oncology research for the summer. Neuroblastoma, medulloblastoma, rhabdomyosarcoma, and desmoplastic small round cell tumors overexpress human epidermal growth factor receptor II (HER2) and cluster of differentiation (CD24) on their surface. Radioimmunotherapy targets those antigens using antibodies. Radioisotopes bound to those antibodies kill the cells. Radioimmunotherapy causes toxicity to normal tissues. Two step pre-targeted radioimmunotherapy reduces this by allowing excess antibody to clear from normal tissues before radiation is delivered. This is further optimized by the self-assembling and disassembling (SADA) antibody platform. Antibodies aggregate within the tumor and disperse outside of the tumor. Therefore, antibodies bound to the tumor remain in the body longer while excess antibodies are cleared faster. This study will compare two-step pretargeted radioimmunotherapy with the SADA platform to one-step radioimmunotherapy against tumors with HER2/CD24 via laboratory testing and a model study. This work is being completed under the mentorship of Dr. Nai-Kong Cheung.

This grant funds a student to complete work in pediatric oncology research for the summer. Infant acute lymphoblastic leukemia (ALL) is a fast-growing blood cancer often caused by changes in the KMT2A gene, which helps leukemia cells survive and spread. This gene creates harmful fusion proteins that work with a partner protein called menin to keep the cancer growing. New drugs like Revumenib block menin and have shown promise in adults, and a clinical trial is testing whether they can help infants whose leukemia has returned or resisted treatment. To better understand how the drug works, Dr. Ernst and her team are developing a novel B-cell acute leukemia model to study the disease more closely. This model allows them to compare what happens when menin is completely removed versus when it is only blocked by the drug. By studying these cancer cells using advanced gene analysis, they hope to find differences that explain why some cases resist treatment. This research could help doctors use menin-blocking drugs more effectively for infants with aggressive leukemia. This work is being completed under the mentorship of Dr. Patricia Ernst.

This grant funds a student to complete work in pediatric oncology research for the summer. This project aims to discover new therapies for an aggressive childhood blood cancer (leukemia). They will focus on KMT2A-r leukemia, which is caused by an abnormal fusion protein involving KMT2A and another protein. This fusion protein activates genes that cause leukemia. Unfortunately, KMT2A-r leukemia is refractory to therapy and therefore highly lethal in infants and children. Prior work identified drugs to block proteins that "partner" with the KMT2A-r fusion proteins, including a protein called menin. While this groundbreaking work led to the recent FDA-approval of a new drug, called revumenib, the leukemic cells often develop the capacity to resist the effects of this drug. This projects therefore proposes a novel approach by focusing on HMGA1 proteins as "molecular keys" required by KMT2A-r fusions to "unlock" the genome and activate genes that allow leukemic cells to resist therapy. The St. Baldrick's Foundation Summer Fellow will help test drugs to block HMGA1 function as new therapies for childhood KMT2A-r leukemia. This work is being completed under the mentorship of Dr. Linda Resar.

This grant funds a student to complete work in pediatric oncology research for the summer. The Min and Koschmann groups are developing a new blood test to help doctors track how well treatments are working for children with DIPG, a deadly brain tumor with no cure. Currently, doctors rely on MRI scans, which don't provide enough detail about whether a treatment is effective. This new test will use tiny particles released by tumors, called extracellular vesicles, to offer a simple, non-invasive way to monitor treatment response in real time. If successful, this approach could improve treatment decisions and be adapted for other childhood cancers. This work is being completed under the mentorship of Dr. Jouha Min.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Osteosarcoma is a rare and aggressive bone cancer that affects mostly children and older adults. For decades, effective therapies to treat this disease have been lacking, including novel immunotherapy treatments used for other cancers. To understand this failure, it is necessary to study the interaction between the immune system and the tumor itself. As such, the St. Baldrick's Foundation Summer Fellow has developed a tool to measure the activity of the immune system as the tumor progresses. In this system, cancer cells targeted by the immune system will turn green when visualized under a fluorescent microscopic. This tool will help us understand the behavior of effector T lymphocytes, a key cell population in the human body responsible to kill cancer cells and other foreign cells. As such, this summer project will help us understand unique characteristics of this tumor and accelerate the cause for more effective therapies. This work is being completed under the mentorship of Dr. Tyler Jacks.

This grant funds a student to complete work in pediatric oncology research for the summer. Ewing Sarcoma (ES) is a type of cancer that is usually found in the bones of children, teens, and young adults yet tends to spread to other areas of the body, making it difficult to target and treat. Understanding why this type of cancer develops and why it travels to different areas of the body is crucial in being able to develop new targeted treatments that work more effectively with fewer side effects than standard treatments like chemotherapy, surgery, and radiation. In ES, a specific protein called EWS::FLI1 is not found in normal cells. This protein does not work correctly like normal proteins in normal cells and causes the ES cells to divide and grow uncontrollably, creating tumors. If the broken protein in ES cells could be turned off with a new medication, it would stop the ES cells from growing into tumors and spreading in the body, stopping the disease. Ideally, the medication would only work in ES cells but so the patient would not experience side effects from the medicine. This work is being completed under the mentorship of Dr. Jeffrey Toretsky.

This grant funds a student to complete work in pediatric oncology research for the summer. The team will identify factors for metastasis at primary childhood cancer diagnosis, as metastases account for 2/3 of cancer-related deaths. By uncovering these factors, they seek to promote early detection and ultimately reduce cancer mortality. Additionally, they aim to investigate factors influencing survival in pediatric patients with metastatic cancer, with a particular focus on socioeconomic determinants such as neighborhood income and education levels. The findings will help identify high-risk populations and inform strategies to prevent poor outcomes. Their approach will integrate traditional epidemiology methods with artificial intelligence techniques to develop an optimal predictive model. In the future, this model can be used to estimate an individual's metastasis risk before it occurs using patient information inputs. Overall, this study aims to advocate for more sophisticated methods to generate clinically meaningful insights and reduce pediatric cancer deaths in society. This work is being completed under the mentorship of Dr. Kim Johnson.

This grant funds a student to complete work in pediatric oncology research for the summer. Two highly aggressive brain tumors, Atypical Teratoid/Rhabdoid Tumors and Embryonal Tumor with Multilayered Rosettes have extremely low survival rates. These tumors arise from a change in normal brain cells that cause uncontrollable growth and tumor development. Inhibiting specific pathways that are important in tumor growth will prevent the tumor development. To test this hypothesis, the team will perform multiple tests using cells from patients tumor cells growing in the lab. Testing how healthy the cells are, how they grow in their life cycle, and how they respond to being treated with a drug. Further, looking at specific proteins a part of these tumors and how they can help inform treatment for patients. These results may lead to a possible early-stage treatment option for patients affected by these cancers. This work is being completed under the mentorship of Dr. Giselle Saulnier Sholler.

The ultimate goal of this project is to define the safest, most effective therapies for children and young adults with Langerhans cell histiocytosis (LCH), which aligns with St. Baldrick's mission to find cures for childhood cancers and give survivors long and healthy lives. LCH is a blood cancer most common in children that creates destructive inflammatory lesions that can be fatal. LCH is caused by mutations activating the MAPK growth pathway in developing blood cells. Current front-line therapy fails to cure over 50% of patients with disseminated disease, and safe and effective options for subsequent therapy is not known. High-dose chemotherapy can be effective, but is toxic. MAPK inhibitor therapy alone does not appear to be durable based on early trials. Dr. Allen and colleagues hypothesize that MAPK inhibition will make cells more sensitive to chemotherapy. Dr. Allen will therefore test safety and efficacy of a new approach of combining chemotherapy with targeted MAPK inhibitor therapy.

The study of genetic disease of cancer predisposition has served as a model for understanding cancer in general. Fanconi anemia is a rare genetic disease of failed blood production and cancer proneness, including leukemia and head and neck cancer. The genes and encoded proteins participate in DNA repair. However, an examination of cancer databases of DNA sequence shows that Fanconi genes are mutated in up to 30% of all head and neck cancers in non-Fanconi patients. Dr. Kupfer and colleagues have studied one particular mutation that resides in the Fanconi FANCD2 gene that interrupts its protein binding to another important gene BLM, which also participates in DNA repair. This proposal will seek to study the normal function of the FANCD2-BLM interaction in the cell and the consequences of its disruption. Dr. Kupfer also seeks to identify ways disruption of the normal pathway will render cancers vulnerable to molecular targeting to improve therapeutics.

Survivors of pediatric brain tumors have a high risk of medical problems that can negatively affect the quality of their lives. Particularly concerning are effects on brain development, including learning and emotional well-being, and metabolism, which can lead to obesity and muscle loss. There is an urgent need for tools that can better predict which children are most at risk so that they can be offered treatments to prevent these problems. Dr. Kann's and colleagues have developed medical imaging tools that use artificial intelligence on routine brain scans to track and predict 1) muscle weakness and malnutrition, and 2) brain development in children. Dr. Kahn and team will test these tools in large datasets from hospitals and clinical trials of pediatric brain tumor patients and survivors to predict the risk of these negative effects in each patient. The tools developed may be used in clinical trials to improve quality-of-life for childhood brain tumor survivors.

Diffuse midline glioma (DMG), previously known as diffuse intrinsic pontine glioma (DIPG), is a deadly childhood tumor with no effective treatments. Dr. Li's project seeks to understand the genetic and epigenetic dysregulation of DMGs. Through cutting-edge single-cell analyses and advanced AI models, researchers aim to map the tumor's epigenetic landscape, identify key regulatory elements, and predict the function of risk mutations. This knowledge could pave the way for new targeted therapies and improve DMG outcomes.

This grant is funded by and named for #Joe Strong 71, a St. Baldrick’s Hero Fund created in memory of Joe Purdue. Joe was a talented football player and cherished friend and son. He was diagnosed with DIPG shortly after graduating from high school, cutting short his plans to attend college. He is remembered for determination as he battled the most lethal form of brain cancer. #Joe Strong 71 carries on Joe's legacy by funding research for DIPG.

Children everywhere in the world get cancer but their chances of surviving differ based on where they live. Disparities in childhood cancer diagnoses and survival have been described by sex and age, but there are gaps in this literature from countries with limited resources. The first goal of Dr. Force's project is to analyze how childhood cancer diagnoses and survival differ by sex, age, and world region, using data from the most comprehensive international collection of hospital cancer registries, and to assess potential underlying drivers of these disparities, which would be beneficial in identifying interventions to improve equity in childhood cancer outcomes. The second goal of Dr. Force's project is to compare childhood cancer data from hospitals and population-based cancer registries, to determine whether hospital data could be used to supplement information on childhood cancer burden where data is currently lacking in global models, better illuminating the disparities that exist globally.

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer with more than 3000 children/adolescents under the age of 20 diagnosed with ALL each year in USA. ALL affects a type of white blood cells called lymphocytes that help the body fight infection and disease. ALL can be broadly divided into either B-ALL or T-ALL. B-ALL affects a type of lymphocytes called B-lymphocytes whereas T-ALL affects T lymphocytes. Historically children with T-ALL have worse prognosis than B-ALL. B-ALL also have better therapeutic options whereas children with T-ALL are limited to therapies with well documented long-term negative effects like chemotherapy, radiation therapy. In this proposal, Dr. Thansapani and colleagues aim to evaluate a new therapeutic approach of nutrient deprivation to treat T-ALL grounded on their strong preliminary finding that T-ALL cells need high levels of the nutrient valine for their growth and survival. Dr. Thandapani's project investigates different avenues exploiting this vulnerability.

Ewing sarcoma (EwS), the 2nd most common childhood bone sarcoma, is an aggressive tumour that primarily affects children, adolescents, and young adults. When EwS tumor cells spread to other parts of the body, known as metastasis, survival is drastically diminished to only 15-20%, which has not changed for decades. Immunotherapy empowers a patient’s own immune system to attack cancer, which has tremendous promise as an alternative to chemotherapies that are often toxic, especially to a growing child. Dr. Sorensen and his team recently identified a protein that is highly expressed on the surface of EwS cells, while showing only minimal to absent expression in normal tissues, nominating IL1RAP as a very promising therapeutic target. With their collaborators at the University of Pittsburgh, they have identified specific antibodies binding to IL1RAP and have engineered these antibodies to be conjugated to a drug that kills EwS cells potently. In this project, they will perform the extensive validation of these compounds to enable the design of early clinical trials for the treatment of EwS. This Better Ewing Sarcoma Therapies (BEST) grant is supported by a unique partnership of funders through the St. Baldrick’s Foundation: D-Feet Cancer, The Faris Foundation, The Shohet Family Fund for Ewing Sarcoma Research, an anonymous donor, and the family and friends of Martha Riedel.

Children, adolescents and young adults with recurrent or refractory Osteosarcoma have a very poor prognosis, with a dismal 6mo overall survival of less than 5%. Presumably, this poor prognosis is in large part secondary to the development of resistance to chemotherapy and radiation. More recent studies employing therapies that release and activate the patients’ immune cells, called T-cells, and even targeted T-cells have not improved this poor prognosis. Dr. Cairo proposes to investigate novel and innovative methods of combinatorial immunotherapy to circumvent known mechanisms of resistance. Together with colleagues, he proposes to investigate at the bench (in the laboratory) and in models with osteosarcoma alternative methods of combination immunotherapy including natural killer cells (NK) that we have been engineered in the laboratory to also circumvent mechanisms of resistance and to additionally express a single or dual target that are present on the osteosarcoma cells.

They further plan to investigate the efficacy of adding other immunotherapies to enhance the function and persistence of these targeted NK cells with antibodies, and two different NK activating cytokines. They will also investigate the optimal combination of this immunotherapy in children, adolescents and young adults with recurrent or refractory osteosarcoma to determine the safety and efficacy of this approach. Finally, Dr. Cario and team will determine what are the genetic and immune mechanisms of resistance after these novel combinatorial immunotherapy approaches utilizing state-of-the-art laboratory techniques. The goal of this grant is to develop novel combinatorial immunotherapy that will significantly increase the overall survival in children and adolescents with poor risk osteosarcoma.

To make a significant impact for kids fighting osteosarcoma, five funders have banded together with St. Baldrick’s to support this grant – The Helping Osteosarcoma Patients Everywhere (HOPE) Super grant supported by Battle Osteosarcoma, the Faris Foundation, the Zach Sobiech Osteosarcoma Fund of Children’s Cancer Research Fund, the Children’s Cancer Fund NY (supporting the Maria Fareri Children’s Hospital and New York Medical College) and Nationwide Children’s Hospital.

CAR-T cell immunotherapies, treatments that use T cells constructed to recognize tumors and kill them, revolutionized how doctors treat children with B cell leukemia (B-ALL). These killer T cells recognize a specific protein expressed on the surface of the leukemic cells. Unfortunately, leukemia frequently relapses and often finds ways to "switch off" the expression of this protein, making T cells unable to track and kill them. This notion is called "antigen escape," as the tumor finds a way to escape the immune treatment. Dr. Aifantis plans to identify ways to avoid antigen escape by boosting the expression of the surface recognition protein. The study aims to validate such mechanisms in an organism using CAR-T cell models and sequencing patient cells. At the same time, Dr. Aifantis will design screens that will help identify surface antigen-specific regulators, so researchers can one day create combinatorial protocols using CAR-T cells and targeting specific antigen surface expression regulators.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Malignant Germ Cell Tumors International Consortium (MaGIC). For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Malignant Germ Cell Tumors International Consortium (MaGIC). For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.