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Dr. MacDonald and colleagues have developed a new test that detects cancer cells in the blood and other fluids of patients with brain tumors. They have discovered that children with a particular type of brain tumor often have cancer cells in their blood. They can also use their test to follow how treatment changes the number of cancer cells in the blood to find out if the treatment being given is working to kill all the remaining cancer cells in the brain. This is the first time such a test has been able to do this using a simple blood draw. Dr. MacDonald and colleagues will use their test for children with other types of brain tumors. Dr. MacDonald and team will study the cancer cells in the blood to see why and how these brain cancer cells are still alive after treatment. This will help to identify the "steps" in which the cancer cells take to avoid being killed by the treatments being given and ultimately will then lead to new treatments targeting these steps to cure childhood brain tumors.

Children with a brain tumor diagnosis face the daunting prospect of surgery, radiation and chemotherapy. While these treatments can be successful, some brain tumors continue to grow and spread in the brain, which can make them impossible to treat. In addition, current treatments can adversely impact a child's cognitive, emotional and physical well-being. New treatments against the most aggressive brain tumors to reduce the burden of tumors in children and increase their quality of life are needed. Dr. Stewart and colleagues will develop new technologies and test new drugs that will allow to rapidly transplant patient tumor cells into models to make hundreds of model avatars that can then be treated with a panel of drugs to identify the most effective treatments for a child's specific tumor, focusing on very aggressive tumors first. Dr. Stewart and team expects this information will be used to help guide doctors decisions on the best treatment options to eliminate the child's tumor and minimize side effects.

One in three children with newly diagnosed cancer has unmet resource needs such as food, housing, transportation, or utilities. These social needs increase during cancer care and are linked to worse outcomes for children and their parents. Government benefits such as the Supplemental Nutritional Assistance Program (SNAP or food stamps) improve child and maternal health outcomes. Dr. Umaretiya will conduct a pilot study using ASSIST, (a benefits navigator intervention to help families enroll and stay on government benefits such as SNAP) among 40 families of children with newly diagnosed cancer and test whether it is feasible and acceptable to families, allowing to identify barriers and facilitators to use ASSIST intervention.

Children diagnosed with a brain tumor called diffuse midline glioma (DMG) have no options for a cure. Dr. Ramakrishna and team at Stanford Medicine have developed a new treatment, called CAR T cells, for these children by training their immune system to find and kill cancer cells. Excitingly, children treated on a clinical trial with these CAR T cells have improved symptoms and reduced tumor sizes. Unfortunately, for some patients, tumors grew after treatment, suggesting a need to understand how to improve the treatment. An immune cell, called a myeloid cell, was identified surrounding treatment of the first patients. Dr. Ramakrishna and colleagues will seek to understand these myeloid cells in the context of CAR T cell activity in patients. Modeling these myeloid cells in the lab, Dr. Ramakrishna and team will test approaches to improve CAR T cell activity against DMG cells. This project will improve understanding of CAR T cells in patients and develop new treatments for children with these devastating brain tumors.

Sneha Ramakrishna, MD, is a pediatric hematology-oncologist at Stanford Medicine Children’s Health and an assistant professor - University Medical Line in Pediatrics - Hematology & Oncology at Stanford Medicine.

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.

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. The Kohanbash lab is investigating how B cells, a critical part of the immune system, function in aggressive brain tumors in children. B cells produce antibodies to fight infections or cancer and carry unique surface markers called B cell receptors, which help them recognize and respond to specific threats. However, in cancer, B cells may behave unpredictably, sometimes helping the body fight against tumors, but in other cases, supporting tumor growth. By examining the specific features of B cell receptors in pediatric high-grade gliomas, they aim to better understand how these immune cells influence tumor development and progression. The goal of this project is to learn more about how the immune system responds to brain tumors in children and how altering these responses could lead to more effective treatments. Ultimately, this research hopes to improve therapies and outcomes for children diagnosed with deadly brain tumors, offering them better chances for recovery and long-term well-being. This work is being completed under the mentorship of Dr. Gary Kohanbash.

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. 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. 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. 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 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 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. 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 a student to complete work in pediatric oncology research for the summer. Childhood brain tumors like Diffuse Intrinsic Pontine Glioma (DIPG) are difficult to treat, especially when they have mutations in a gene called TP53. These mutations make cancer cells resistant to radiation, which is the main treatment for DIPG. With support from the St. Baldrick's Foundation, the summer student researcher is working with Dr. Blackburn's team to study whether existing drugs can help radiation work better in TP53-mutant tumors. Using zebrafish, they have identified several promising drugs and will now investigate how they make cancer cells more vulnerable to treatment. This research could help lead to better therapies for children with DIPG. This work is being completed under the mentorship of Dr. Jessica Blackburn.

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. Neuroblastoma, a pediatric solid tumor, has a poor prognosis in cases with MYCN proto-oncogene amplification requiring novel therapeutic strategies. Although immune checkpoint inhibitors have shown dramatic effects in adult cancers, their efficacy in neuroblastoma is limited due to its immunosuppressive tumor microenvironment (TME). To address this, the Weiss lab developed a novel neuroblastoma model (Mycn-nGEMM) to study immuno-oncology. They identified that macrophage migration inhibitory factor (Mif), a cytokine with pro-tumorigenic properties, is highly expressed in both human and mouse neuroblastoma tumors. Furthermore, Mif inhibition was found to reduce immunosuppressive tumor-associated macrophages (TAMs),, suggesting that targeting Mif could enhance anti-tumor immunity in neuroblastoma. The St. Baldrick's Foundation Summer Fellow will investigate Mif's role in TAMs and the TME using genetic and pharmacological approaches to reveal the immunosuppressive mechanisms of neuroblastoma. This work is being completed under the mentorship of Dr. William Weiss.

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. 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.