Grants Search Results

Dr. Stanton and colleagues are developing new approaches to understand how DNA is organized for gene expression in a lethal childhood tumor called rhabdomyosarcoma (RMS). In RMS, the standard of care therapies haven't changed substantially in 40 years and patient outcomes haven't improved greatly during this time. New approaches are desperately needed. There is a lack of a fundamental understanding of the mechanisms for how the cancer-causing genes function in RMS. Dr. Stanton and his team are integrating cutting edge approaches in synthetic biology, modeling, and genomics to understand how and why RMS forms, with the granularity of single gene targets for mechanism studies. Through Dr. Stanton's studies, the community will gain an understanding of how the cancer-causing genes are altering the organization of DNA in RMS cells.

This grant is funded by and named for the Aiden's Army Fund, a St. Baldrick's Hero Fund. Aiden Binkley who was diagnosed with Stage IV rhabdomyosarcoma at age 8. This bright, funny and courageous little boy believed he got cancer so he could grow up to find a cure for it. His vision is being carried on by Aiden’s Army through the funding of research. They will march until there is a cure!

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.

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.

Each year, approximately 1,000 Americans aged 20 years or younger are diagnosed with acute myeloid leukemia (AML). Currently, no drugs can eradicate all AML cells in pediatric patients, and cells remaining after treatment often cause disease recurrence and poor survival. Dr. Li and colleagues have found that two mitochondrial enzymes that function in energy metabolism, known as DHODH or SDH, shield leukemia cells from eradication by immune cells. Dr. Li will use models relevant to pediatric AML to ask how these factors block anti-cancer immune responses and test effectiveness of a first-in-class leukemia cell-specific DHODH inhibitor combined with existing immune therapy in eradicating AML. If successful, this study will lead to development of new anti-leukemia drugs that could approach a cure for childhood AML.

Neuroblastoma (NB), a cancer that commonly affects young children, often presents with aggressive clinical behavior and poor prognosis, making the identification of effective therapeutic targets essential. NB is known for its resistance to conventional chemotherapy, and one of the mechanisms contributing to this resistance is the activation of a key regulator of gene expression, known as 'NF-kB’. NF-kB activates the expression of genes that contribute to NB survival. NF-kB also plays a role in promoting spread of NB to other parts of the body (e.g. bone marrow, liver, and lymph nodes). Because of its critical role in regulating survival, inflammation, and metastasis, NF-kB presents an attractive target for novel therapeutic strategies in NB. Inhibition of the NF-kB pathway can potentially sensitize NB cells to chemotherapy, reduce tumor growth, and inhibit metastasis. Dr. Letterio and colleagues will explore the activity of a new class of drugs (known as SOTs), that are potent inhibitors of NF-kB.

This grant is named for David's Warriors, a St. Baldrick's Hero Fund. The fund was created in memory of David Heard who battled neuroblastoma until his passing at the age of ten. David inspired his family and countless others to commit to raising money for research to fight pediatric cancer through the St. Baldrick’s Foundation. The Fund honors the amazing spirit with which he lived, embracing life until the very end.

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.

Brain cancer is the leading cause of cancer-related deaths in children, highlighting the urgent need for more effective treatments. While chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for children's blood cancers, it has shown limited success in brain tumors. Dr. Huang and colleagues will initiate a phase I trial in children with HGG and DIPG to assess safety and immune effects utilizing the understanding that CD70, a protein driving tumor growth, is a promising CAR T-cell target for high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG).

A subset of deadly pediatric cancers, known as sarcomas, are caused by a mysterious, mutated protein called CIC::DUX4. Treating this disease is very difficult, in part because little is known about its biology. The teams of Dr's. Wood and Hendrickson have assembled the world's best collection of CIC::DUX4 laboratory models, using them to discover that CIC::DUX4 sarcomas require a protein called COP1 for their survival, whereas normal tissues in bodies do not. Dr. Wood and colleagues will perform studies to understand how well future drugs targeting COP1 will work as therapies for this deadly disease while defining why this disease needs COP1 in the first place. Together, these studies will identify a highly promising new therapeutic strategy for CIC::DUX4 sarcoma while also revealing insights that could lead to additional new types of drugs for this disease.

Ewing sarcoma commonly appears in a bone among patients between 10-20 years old. About 25% of patients present with a clinically detectable metastatic disease. Despite aggressive chemotherapy and radiation, almost no improvement has been seen in patients with metastatic disease (80% mortality). The failure to stop Ewing's sarcoma metastasis is partially due to the lack of understanding about the molecular pathways that regulate its spreading. Dr. Yang and colleagues will study several upstream regulatory genes of TWIST1 in Ewing sarcoma metastasis and test whether drugs targeting these genes will block metastasis with higher specificity and fewer side effects than conventional therapy. In the long term, this research will lead to novel therapeutic regimens for Ewing sarcoma metastasis.

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. 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.

Spitz tumors are rare skin growths that occur in children and share some features with melanoma, a type of skin cancer. However, Spitz tumors often behave differently than melanoma, with many appearing harmless even if they spread to nearby lymph nodes. This makes diagnosing and treating them particularly challenging. Some Spitz tumors can resemble melanoma in their aggressive behavior, while others remain indolent, causing uncertainty about how they will progress. This research focuses on understanding two key aspects of these tumors: First, Dr. Boris and colleagues aim to determine whether Spitz tumors spread widely and early in their development. Second, they will investigate whether the immune system plays a critical role in controlling these tumors. Spitz tumors often contain unique genetic changes leading to fusion proteins, which may act as signals that the immune system can recognize and target. To study this, Dr. Boris will collect blood samples from children with Spitz tumors and analyze them for traces of tumor DNA, which could indicate how widely the tumors have spread and if they persist in the body after surgery. Additionally, they will study how the immune system interacts with these tumors by identifying specific markers on the tumor cells and testing whether the patient’s immune cells can recognize and respond to them. This multidisciplinary team includes experts in melanoma, pediatric dermatopathology, and immune system research, all of whom are dedicated to improving the care of children with Spitz tumors. By uncovering how these tumors behave and how the immune system interacts with them, the aim is to develop better tools for diagnosing and monitoring these tumors, and reduce the need for invasive surgeries.

This grant is funded through a partnership between the St. Baldrick’s Foundation and the Melanoma Research Alliance.

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. 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.