Grants Search Results

Modern pediatric cancer diagnosis requires the ability to perform and interpret molecular studies including gene-specific assays as well as sequencing studies to capture mutations specific to pediatric cancer that are important for diagnosis and treatment stratification. Such assays are widely available in developed countries and most hospitals have trained molecular pathologists who can carry out and interpret these studies. These are highly technical skills that require at least a year of hands-on training. In many Low and Medium Income Countries (LMIC) including Mexico, there are very few trained molecular pathologists, limiting the ability to provide adequate diagnosis for cancer patients. Dr. Ramirez-Ristori will obtain this training at the University of California, San Francisco and return to Mexico to become the very first fully trained molecular pediatric pathologist in the entire country.

This grant funds a student to complete work in pediatric oncology research for the summer. Dr. Satake and colleagues are studying a rare and aggressive childhood kidney cancer called malignant rhabdoid tumor of the kidney (RTK). Children with RTK have extremely poor outcomes (survival rate 25%) despite lots of different treatments since tumors continue to grow even with treatment and tend to relapse. They believe that the investigational drug called OTS964 may be a new potential treatment. They also believe that OTS964 may be even more effective when used with navitoclax, a drug which has a different mechanism of killing cancer cells. In this project They plan to test the new treatment using these drugs in a human RTK mouse model, and to study the mechanism of actions, with the goal of finding a new treatment for RTK patients. This work is being completed under the mentorship of Dr. Noriko Satake.

This grant funds a student to complete work in pediatric oncology research for the summer. B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, affecting over 3,000 children in the U.S. annually. A groundbreaking treatment called CAR T-cell therapy involves collecting a patient's immune cells, engineering them to recognize and kill cancer cells, and reinfusing them into the patient. While effective for many, CAR T-cell therapy often fails over time because the engineered cells can "burn out" or cancer cells change to avoid detection. To solve these problems, Dr. Pulsipher's lab is developing a smarter CAR T-cell system that uses multiple signals to activate, reducing burnout, and targets more than one cancer marker, making it harder for the cancer to hide. If successful, this approach could significantly reduce relapses in B-ALL patients, offering them a better chance at long-term remission. This work is being completed under the mentorship of Dr. Michael Pulsipher.

This grant funds a student to complete work in pediatric oncology research for the summer. Currently, developing a cancer drug in the lab and bringing it to the clinic takes years or even decades to accomplish. Although many initial drugs are promising candidates, they ultimately fail because they have no effect, off-target effects, or are simply too toxic. One exciting avenue for cancer treatment involves modifying a patient's immune cells by adding chimeric antigen receptors (CARs) to their surface. Peptide-centric CARs (PC-CARs) can recognize protein fragments called peptides on the surface of cancer cells, which originate from cancer proteins within. Dr. Yarmarkovich's laboratory has developed PC-CARs against one of the most common childhood cancers called neuroblastoma and is currently pursuing clinical trials. To rapidly develop new PC-CARs, they have used new advancements in artificial intelligence to redesign their PC-CARs to recognize another upregulated neuroblastoma peptide called CHRNA3. Eventually, their research can be expanded to treating all cancers alike. This work is being completed under the mentorship of Dr. Mark Yarmarkovich.

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. Children diagnosed with diffuse midline glioma (DMG), an aggressive brain tumor, face limited treatment options. A new drug called ONC201 has decreased tumor growth in some patients but not others. This research aims to understand why this difference in response occurs. Researchers have discovered that ONC201 affects how cells modify their genetic instructions (RNA), specifically through a process called m6A modification, which affects thousands of genes. When treating tumor cells with ONC201, this group observed a significant decrease in these modifications. The St. Baldrick's Foundation Summer Fellow plans to help study whether this change happens in all tumor cells or only in those that do not respond well to the drug. By analyzing these samples, they hope to identify markers that could predict which patients will benefit most from this treatment. This knowledge could lead to more effective ways to use ONC201 and help develop better treatments for children with DMG. This work is being completed under the mentorship of Dr. Jessica Foster.

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. Children with aggressive neuroblastoma tumors have poor cure rates despite intensive treatment, and new therapies are needed. Kinases are proteins that control signals in cancer cells leading to cancer cell growth and spread, and we have developed a new drug, getretinib, that inhibits the RET kinase that is important for neuroblastoma tumor growth. This project will test getretinib to determine its effectiveness against neuroblastoma cells and tumors, and evaluate cells before and after treatment with getretinib to determine how getretinib kills neuroblastoma cells and to identify specific genes and proteins that are important for neuroblastoma cell responses and resistance. The results of these studies will determine whether and why getretinib is effective against neuroblastoma, leading to clinical trials using new drugs directed against RET for treatment of children with neuroblastoma. This work is being completed under the mentorship of Dr. Pete Zage.

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 an undergraduate student to complete work in pediatric oncology research for the summer. The St. Baldrick's Foundation Summer Fellow in the Goldsmith Laboratory at Emory University is working to develop new cell-based immunotherapies for neuroblastoma. They work alongside a team of researchers seeking to apply the unique properties of gamma delta T cells as an effective, off-the-shelf adoptive cell therapy for children with neuroblastoma. During the summer fellowship with St. Baldrick's Foundation, the student will investigate the expansion and anti-neuroblastoma activity of a specific type of gamma delta T cell called the VD1 subset. This work is being completed under the mentorship of Dr. Kelly Goldsmith.

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.

This grant funds a student to complete work in pediatric oncology research for the summer. Pediatric sarcomas are devastating childhood cancers. New therapies that have fewer side effects but can more effectively kill cancer cells are urgently needed. There are multiple factors that make pediatric sarcomas hard to treat. One of those reasons is that not all pediatric sarcoma cells are like each other. Some grow very fast, whereas some others grow more slowly but can migrate and form metastases. Dr. Langdon's laboratory is working on developing combination therapies that can limit the impact of all the different types of pediatric sarcoma cells. During the next summer, the St. Baldrick's Foundation Summer Fellow's project will be to discover reasons why these combinations work so well against pediatric sarcoma cells. They will also learn several new techniques and gain experience in mentoring and more effective communication strategies. This work is being completed under the mentorship of Dr. Casey Langdon.

Cancer patients take life-saving drugs that, unfortunately, can result in peripheral nerve damage. For example, many patients receiving cisplatin experience permanent hearing loss. There is one therapy that has been approved to mitigate cisplatin-induced hearing loss, however, the reduction in hearing loss is modest (< 30%) and this mitigating treatment is associated with poorer overall survival rates due to inhibition of cisplatin's cancer-fighting properties. Thus, it is approved for low-risk pediatric patients only. To develop a better alternative, Dr. Rutherford and colleagues are testing novel compounds they have developed at Washington University, which have shown to protect the ear from noise trauma. With hearing tests and with anatomical measurements of the cochlea, Dr. Rutherford will attempt to prevent hearing loss following cisplatin treatment in models. After this innovative project proves successful, subsequent model studies will determine if Dr. Rutherford's therapy inhibits cisplatin's cancer-fighting role.

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.

Brain tumors are the leading cause of cancer related death in children. The outcomes for high-grade gliomas in children are dismal. Chimeric antigen receptor (CAR) T cells are genetically engineered cells programmed to target cancer cells with high precision. The application of CAR T cells in brain tumors in children is still limited compared to leukemia. One challenge is that CAR T cells need multiple hits to kill brain tumor cells compared with leukemic cells, where a single hit is sufficient. Dr. Abu Arja and team discovered a subset of CAR T cells that are more potent and can more proficiently kill brain cancer cells by increasing their lethality, making a second hit unnecessary. In this project, Dr. Abu Arja is studying the cellular program of this unique subset of potent killer CAR T cells to better understand why they are superior killers. Dr. Abu Arja plans to use these findings to genetically engineer new enhanced CAR T cells to eliminate tumors in children with brain cancers.

The first year of this grant is funded by and named for the Be Brooks Brave Fund. Despite his diagnosis at age 5 with inoperable brain and spinal tumors, Brooks taught so many people what life is truly about--love. He was BRAVE beyond his years with an inspiring “faith over fear” attitude. This Hero Fund hopes to raise money for high-grade glioma research so no other family will hear the words, “there is no cure”.

Neuroblastoma is a devastating pediatric cancer, with only 50% survival in aggressive "high-risk" disease. Survivors are burdened with life-long side effects from chemotherapy and radiation. Newer therapies, such as cancer vaccines, provide an opportunity to mobilize a patient's own immune system to find and destroy cancer cells. Identifying the unique genetic signature of an individual patient's tumor allows scientists to formulate a personalized vaccine to stimulate the immune system to recognize tumor-specific mutations, called "neoantigens". Dr. Spear has developed a new tool to identify these unique genetic signatures (neoantigens) and test the effectiveness of the neoantigen vaccine in modes. These findings will lay the groundwork to develop a clinical trial using personalized vaccines for high-risk neuroblastoma and other pediatric cancers.

This grant is funded by and named for the Arden Quinn Bucher Memorial Fund, a St. Baldrick's Hero Fund. Arden’s intelligence, empathy, and dynamic personality charmed everyone and is now her legacy. Before her neuroblastoma diagnosis on October 11, 2007 at age two, she happily played with boundless energy and imagination. Even throughout her difficult months of treatment, Arden bravely managed to keep smiling and learning. This fund supports St. Baldrick’s mission: funding the most promising research, wherever it takes place to provide kids fighting cancers less toxic, more effective treatments allowing them to live longer, healthier lives.

Leukemia and lymphoma are blood cancers that are a major cause of death in children. Many of these cancers are curable with chemotherapy, but in some people the cancer comes back and is harder to cure. A new treatment called CAR-T cells involves genetic engineering of a cancer patient's own immune system cells to fight cancer, and can cure many people. However, this treatment still does not work well enough in about half the people who get it. Dr. Pauerstein proposes improving the sensitivity of CAR-T cells to cancer using engineered cell adhesion molecules, a type of molecular glue between two cells. CAR-T cells do not attach to cancer cells as strongly as normal T cells do, and this limits their ability to find and kill cancer cells. An engineered adhesion will be used in combination with CARs to improve the ability of CAR-T cells to kill cancer. Dr. Pauerstein and team will also study how changes in cell adhesion affect how CAR-T cells kill cancer. This work should improve cell-based treatments for blood cancers.