Grants Search Results

Diffuse midline glioma is a devastating disease with no known curative therapy. New treatments using immunotherapy approaches, like CAR T therapy, show promise; however, tumors often escape detection by hiding their target proteins and suppressing the immune response to therapy. Dr. Pomaville seeks to tackle this problem by manipulating RNA modifications in the tumor and body to improve response to CAR T therapy. She has found that drugs that mediate RNA methylation, the most common modification on protein-coding mRNA, increases protein levels of existing CAR T antigens and can induce cell death. This RNA modification mark also influences how the body's immune system responds to tumors. Dr. Pomaville will test this drug in cell-line and immunocompetent models to assess whether manipulation of RNA methylation leads to improved efficacy of CAR T therapy. Dr. Pomaville and team will develop combination strategies that enhance the response to immunotherapy in patients. This grant was awarded at Children's Hospital of Philadelphia and transferred to Seattle Children's Hospital.

This grant is funded by Allied World, a global provider of insurance and reinsurance solutions.

Ewing sarcoma is a deadly cancer that affects children and young adults. Dr. Gao and team know that these cancer cells depend on a special protein, ETV6, to stay alive. Certain natural fats inside the cell can weaken this protein and slow the cancer's growth. Dr. Gao and colleagues will learn exactly how these fats affect the cancer cells and will search for medicines that safely increase these fats to damage the tumor. Dr. Gao's research will open the door to new and gentler treatment options for children with Ewing sarcoma.

This grant is made possible through funding from D-Feet Cancer, The Dalton Fox Foundation and named in memory of Dalton, who is the inspiration for the Foundation that is lovingly led by his parents and sister. Dalton loved to tell good jokes and had a contagious sense of humor that lit up any room he walked into. Even on his worst days, he inspired his community and family with his positive outlook. He loved baseball, swimming, fishing and watching Marvel movies and while his time here was much too short, his memory continues to motivate so many. The Foundation is focused on fueling more research for Ewing sarcoma.

This grant funds a student to complete work in pediatric oncology research for the summer. Medulloblastoma is the most common malignant brain tumor in children, and the Group 3 subtype is especially aggressive because it spreads early and often returns after treatment. Dr. Hu and colleagues will study a gene called SMARCD3, which normally helps guide how young brain cells grow, mature, and move to the right places as the brain develops. Dr. Hu believes Group 3 tumors hijack this normal developmental program to help cancer cells spread, and that lowering SMARCD3 may shift this tumor toward a less aggressive state. By studying SMARCD3 in models of brain development and tumor formation, Dr. Hu and colleagues will test whether targeting this pathway will reduce tumor spread and improve outcomes for children. This work is being completed under the mentorship of Dr. Baoli Hu.

Dr. Kagami is developing LBSeq4Kids, a novel liquid biopsy test designed specifically for children with cancer. Traditional biopsies are invasive and only provide information from one point in time. In contrast, liquid biopsies use samples of body fluids - such as blood, spinal fluid, or fluid from the eye - to detect tumor DNA in real time. While this method is used in adult cancers, it is not widely available for children due to smaller sample volumes and the genetic variety of tumors. Dr. Kagami and colleagues are developing and clinically validating a three-part testing platform. LBSeq4Kids will help to better personalize treatment and monitor how a child's cancer responds to therapy. This project will also help determine which liquid biopsy tests and body fluids provide the most useful information for different cancers and stages of treatment. The goal is to improve diagnosis, guide more effective targeted therapies, and support better long-term outcomes for children with cancer.

This grant is funded by Allied World, a global provider of insurance and reinsurance solutions.

Germ cell tumors can occur in children, adolescents, and young adults. Remarkably, these cancers begin in the fetus, before birth. About 10,000 new germ cell cancers are diagnosed annually in the US, and the incidence is increasing. An individual's genetic make-up, early development, and environmental exposures all affect the risk for germ cell cancer, but the underlying mechanisms are poorly understood, due in part to a lack of research models. Dr. Weiss and colleagues will use a model that accurately recapitulates germ cell cancers and will test how risk factors, including both genetic and developmental factors, promote germ cell cancers to study environmental factors like forever chemicals and pesticides that have been linked to increased germ cell cancer incidence. By testing risk factors and understanding how they act, Dr. Weiss and colleagues will identify new approaches to detect and prevent these cancers in pediatric and young adult populations.

MLL (Mixed Lineage Leukemia)-rearranged leukemias are one of the most prevalent childhoods leukemias and carries poor to intermediate prognosis. Current therapy is still inadequate for MLL-rearranged (MLLr) leukemias, highlighting the need to develop better therapeutics. A protein complex that helps to rearrange the packing of genomic DNA within the cell, the BAF chromatin remodeling complex, is vital for MLLr leukemia cell survival. In addition, loss of BAF complex has also been shown to boost anti-tumor immunity in previous published studies. Dr. Zhu and colleagues will target BAF complex leads to dual effects of eradicating leukemia cells, boosting anti-tumor immunity which synergizes to curb leukemia. Dr. Zhu and colleagues' research will identify a novel dual acting therapy for MLLr leukemia.

This grant is funded by and named for Emily Beazley's Kures for Kids Fund, a St. Baldrick's Hero Fund. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma and battled through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle, inspiring a community to come together to show love and change lives. She had a dream of starting a foundation to fund research and named it “Kures for Kids”. Today, Emily's family and friends carry on her dream and her mission in her memory.

This year, neuroblastoma will account for approximately 15% of cancer-related deaths in children. Despite recent advances in treating high-risk neuroblastoma, nearly half of patients will relapse with no curative treatments. Thus, safe and effective treatments are urgently needed. Using recently developed tools to find new therapy targets at a large scale, Dr. Mabe and colleagues understand that neuroblastoma tumors require polycomb repressive complex 1 (PRC1). Dr. Mabe and colleagues will identify that a new class of drugs that blocks PRC1 activity can reduce neuroblastoma tumor growth. To determine the exact mechanism by which these drugs reduce neuroblastoma growth, Dr. Mabe's lab will apply sequencing technologies to assess how PRC1 changes the neuroblastoma tumors to become less like a cancer cell and more like nerve cells.

Ewing sarcoma (EwS) is a bone and soft tissue tumor that most commonly affects children and young adults (AYA). Patients with relapsed/refractory (R/R) EwS continue to face dismal outcomes. While chemotherapy backbones are effective in patients with R/R EwS, outcomes are insufficient, and there is a need to identify combination strategies with novel agents to improve outcomes. Dr. Ganapathi and colleagues have found that EwS is critically dependent on the menin protein, which cooperates with the fusion protein EWS::FLI1 to drive growth and metastasis. Lab and model studies show that blocking menin with Revumenib (FDA approved for pediatric leukemias) powerfully suppresses tumor invasion and metastasis. Dr. Ganapathi and lab will conduct an early phase clinical trial of Revumenib combined with chemotherapy. This combination will ultimately improve outcomes for patients with R/R EwS.

This grant is generously supported by JC Strong, a St. Baldrick’s Hero Fund, established in honor of Jackson Kalbhenn to celebrate his survivorship. Jackson was 5 years old when he was diagnosed with Ewing sarcoma. After 14 cycles of aggressive chemotherapy, 69 nights in the hospital, and a resection on his left leg, his treatment was complete. Today, Jackson shows no evidence of disease and enjoys an active life filled with all things sports related. Through JC Strong, his family hopes to make meaningful difference for every child and family facing Ewing sarcoma.

Vincristine is a common and effective chemotherapy for children with leukemia, sarcomas, and brain tumors. Unfortunately, many children who receive it develop nerve damage that cause pain, tingling, and long-term disability. There are currently no treatments that prevent this side effect. To understand why this nerve damage occurs, Dr. Gomez Deza and colleagues use cell models (derived sensory neurons that closely mimic how children's nerves respond to vincristine). Using a large genetic screen, Dr. Gomez Deza and team will use a molecular regulator that functions as a key switch helping drive nerve injury. Blocking this pathway protects nerve cells in the lab, reduces pain-related behaviors in models, and does not interfere with vincristine's ability to fight cancer. Dr. Gomez Deza and colleagues will uncover how this pathway controls the harmful stress responses triggered by chemotherapy and will test whether inhibitors already in clinical trials for other uses could serve as protective treatments for children receiving vincristine.

Rhabdomyosarcoma (RMS) is an aggressive childhood cancer that resembles developing muscle but cannot mature. The most dangerous form is driven by the PAX3::FOXO1 gene fusion, which forces uncontrolled growth. Better treatments are urgently needed because current therapy cures fewer than one in three children whose cancer returns. Dr. Khan and colleagues research targets FGFR4, a protein expressed at very high levels in RMS but not in normal tissues. A highly specific antibody against FGFR4 enables precise delivery of drugs into cancers. Dr. Khan and team will use this antibody in two ways: (1) to create an antibody-drug conjugate that delivers a drug blocking EP300, a key partner PAX3::FOXO1 uses to activate cancer genes: and (2) to build an antibody-PROTAC shuttle that brings a protein-destroying drug into FGFR4-positive cells to eliminate EP300. By disabling EP300 only in cancer cells, Dr. Khan and team will halt RMS growth while sparing healthy tissue and pave the way for safer, more effective treatments.

Year 1 of this grant is made possible in part, through funding from The Maddox Potter Foundation and is named in memory of Maddox, who is the inspiration for the Foundation. “Mad Dog” was a beautiful son, devoted big brother, diligent student and accomplished junior golfer. He fought alveolar rhabdomyosarcoma bravely for a year, and his final request was that someone, somewhere, would learn something from him. The Foundation is committed to honoring Maddox’s request by supporting families facing childhood cancer, funding critical research, and connecting the game he loved to hope, purpose, and philanthropy.

Rhabdomyosarcoma (RMS) is a childhood cancer that affects muscle cells which attach to bones, affecting how a child moves, smiles, walks, and performs daily tasks. RMS can be very difficult to cure when it spreads. Children with metastatic or relapsed RMS have poor survival, and current treatments often cause serious long-term side effects including second cancer. New, safer therapies are urgently needed. Dr. Chen and colleagues will work with a gene called BRD1, which helps RMS cells move and invade other tissues. BRD1 controls another gene, MYOG, which is abnormally active in this cancer. When either gene is reduced, RMS cells become much less able to spread. Dr. Chen and colleagues will uncover how BRD1 and MYOG work together to drive metastasis and will identify the genes they regulate to serve as new drug targets. By revealing a new biological pathway that supports tumor spread, Dr. Chen and team will lay the foundation for more effective, less toxic treatments for children with high-risk RMS.

Dr. Boelens and colleagues will study how the immune system recovers after a bone marrow transplant in children with leukemia. These transplants can cure cancer, but some children relapse or develop a serious complication called chronic graft-versus-host disease, where the donor immune system attacks the child's tissues. Dr. Boelens and team will focus on the thymus, an organ that trains new immune cells but is easily damaged by chemotherapy and radiation. Dr. Boelens and colleagues will measure how well the thymus works and how immune cells grow during the first year after transplant. Dr. Boelens will confirm their findings by working with many hospitals through a large pediatric transplant network. By finding early warning signs of poor recovery, Dr. Boelens and colleagues will help doctors identify children at high risk and guide more personalized care so that more children survive transplant and grow up healthy, with fewer long-term complications.

Many children with bone tumors cannot be cured. This is true in particular if the tumor has come back. Dr. Gottschalk and colleagues will use the immune system to fight cancer. In their approach, they will take immune cells from patients and train them in the laboratory to fight cancer. Dr. Gottschalk and team's training methods willl consist of inserting a gene into immune cells that are a called T-cells. Once the cells have completed training in the laboratory, they are given back to patients. A second gene is inserted into T cells so that the T cells can grow better in patients after infusion. Dr. Gottschalk and colleagues will figure out the best structure of the second gene and will perform laboratory studies to determine which T cell works best, resulting in selecting the best T cell product for a future clinical study for children with bone tumors.

Acute myeloid leukemia (AML) is an aggressive and molecularly heterogeneous cancer. Despite recent progress in developing new agents, front-line therapeutic protocols have not changed markedly over the past two decades and are associated with substantial morbidity and mortality. Accordingly, there is a need to develop novel mechanism-based treatments. Pediatric AML patients with NUP98 (nuclear pore complex protein 98) gene rearrangements (NUP98-r) have particularly dismal outcomes, with overall survival rates of 25-35%. Dr. Tian and colleagues are studying important proteins that contribute to a cell's ability to become cancerous in one of the most common types of NUP98-r AML: NUP98::KDM5A. Dr. Tian is also optimizing a compound's ability to directly inhibit KDM5A. Identification of these targets will allow for development of new drugs in the treatment of NUP98-r pediatric AML.

This grant is funded by Allied World, a global provider of insurance and reinsurance solutions.

Pediatric craniopharyngioma (CP) is a rare brain tumor (5-10% of cases). CP is located near vital areas such as the eyes and the hormone control center, and recurs after surgery in 50% of cases. Standard treatments (surgery and radiation) lead to serious issues and reduced quality of life for most patients. No drugs are available for treating CP. Dr. Lee and colleagues will target the Wnt signaling pathway, a system that cells use to communicate and control when they grow or divide in CP tumors when Wnt signaling is overactive. Dr Lee and team will test promising drugs for CP: FDA-approved drug pyrvinium and a newer, unapproved drug SSTC3. These drugs block Wnt signaling and are effective in other cancers. Dr. Lee and team will use CP tumor cells from patients and CP models, and measure how the drugs block Wnt signaling in cells determining if the drugs shrink tumors. Dr. Lee and colleagues will pioneer targeted therapies and reduce the need for harsh CP treatments.

In some children with cancer, their bodies become severely inflamed and they develop a condition known as hemophagocytic lymphohistiocytosis, or HLH, which is often deadly. It is not yet understood why some children with cancer develop HLH and others do not. Dr. Meyer is using advanced technologies to carefully study blood cells from children with cancer who develop HLH. She is also working to create the first model of this disease so that she can better study the underlying disease mechanisms. By increasing our understanding of HLH, she seeks to develop strategies that will help doctors quickly identify affected children and determine which medicines are most effective. Her overall goal is to help more children survive this devastating condition. If successful, her findings will apply not only to HLH, but also to other life-threatening immune system disorders resulting from cancer and/or its treatment.

This grant is funded by Allied World, a global provider of insurance and reinsurance solutions.

Despite advances in pediatric AML treatment, some leukemia cells can temporarily shut down and hide from therapy, later reawakening to cause relapse, the leading reason many cancers return after remission. Dr. Wang and colleagues seek to understand what allows these dormant leukemia cells to evade treatment and how they may eliminate them. Using gene-editing technology, Dr. Wang and team will work with a protein called DDX6, which acts as a key switch that keeps certain genes turned off in active leukemia cells. When DDX6 is lost, cancer cells enter a dormant, treatment-resistant state. This is a promising way to target these dormant cancer cells by blocking a signaling pathway called MEK which makes cells sensitive to chemotherapy. By uncovering how leukemia cells use dormancy to escape therapy and identify a way to target them, Dr. Wang and team's work will lay the foundation for new treatments to prevent relapse and improve long-term survival for pediatric AML patients.

Childhood leukemia happens when certain blood cells grow out of control. Dr. Wang'ondu and colleagues will focus on a protein called IKZF1, a transcription factor that helps young immune cells develop normally. In some children, IKZF1 is altered in a way that disrupts this process and makes leukemia more likely to form. Children whose leukemia has IKZF1 changes often have worse outcomes with current treatments. Dr. Wang'ondu will study how a specific change called IKZF1 N159Y disrupts normal immune cell functions and how Dr. Wang'ondu and team can target it with new types of drugs. Dr. Wang'ondu will work to understand how changes in transcription factors like IKZF1 cause leukemia and will help develop more effective treatments for children affected by these changes.

Neuroblastoma (NB) is a common and deadly solid tumor in children, and despite receiving the most intensive treatments available, 50% of all children with high-risk disease die from this cancer. NB is aggressive in part because it has high levels of chemicals called polyamines (which are made from arginine/ARG). A drug called difluoromethylornithine (DFMO), blocks polyamine production. Dr. Turn and colleagues combine DFMO with decreased ARG to cure 1/3 of models with NB without using chemotherapy in their research. There are however, remaining tumors that have increased macrophages. Although macrophages can eat cancer cells, many of these macrophages are hijacked to help the tumor to grow despite decreased polyamines. Dr. Turn and colleagues will learn how macrophages do this and will find ways to target them to improve this therapeutic strategy in NB.

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.

Dr. Shen will develop a new immune-based approach to treat diffuse midline glioma, a deadly childhood brain tumor with very limited treatment options. Dr. Shen and colleagues' work will focus on helping the body's natural killer immune cells better recognize and destroy tumor cells while sparing healthy brain tissue. Dr. Shen will test whether standard radiation therapy can make tumor cells more visible to these immune cells, thus improving treatment effectiveness and safety. Dr Shen's research will lay the groundwork for a more precise and less toxic therapy for children with this devastating disease.

This grant is funded by and named for Luke's Army Pediatric Cancer Research Fund. This Hero Fund was created in memory of Luke Ungerer who brought smiles and sunshine wherever he went with plenty to share with everyone. He battled a brain tumor with a positive spirit and inspired others with his courage in his short life. This fund intends to carry on Luke’s legacy of positivity with the hope that it will ripple across many lives for many years to come.