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.

Acute myeloid leukemia (AML) is a high-risk blood cancer in children. Even after intensive chemotherapy and bone marrow transplant, small numbers of leukemic cells, called measurable residual disease (MRD), can persist and later cause relapse. Current hospital tests examine large mixtures of cells and can miss these dangerous clones, causing clinicians to underestimate a child's relapse risk. Dr. Furlan and team will apply advanced single-cell genomic technologies to profile tens of thousands of cells from each child, pinpoint rare residual leukemia cells, and define the programs that allow them to survive treatment. Using these insights, Dr. Furlan and colleagues will develop practical, more sensitive MRD assays that children's hospitals could implement to better identify which patients are truly in deep remission and which remain at high risk, guiding earlier intervention and improving long-term cure rates for children with AML.

This grant is generously supported by Super Soph's Pediatric Cancer Research Fund, a St. Baldrick's Hero Fund. Sophie Rossi was diagnosed with AML at 3 months of age. Throughout her courageous battle, she was always smiling, always joyful. This fund was created to honor her spunky, sweet spirit by funding research to find cures for AML and all childhood cancers.

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.

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.

Leukemia is a leading cause of death in children. Exciting new treatment strategies direct immune cells against B acute lymphoblastic leukemia (B-ALL) cells, however they are not effective for many patients, particularly those with relapsed disease. Why these therapies work in some children but not others is not understood. There is evidence that leukemia cells protect themselves by creating an environment around themselves (the immune microenvironment) that inhibits immune cells. Data indicates that B-ALL cells may impair a process called emergency myelopoiesis (EM), inhibiting normal immune cell function, if the leukemia cells express a protein called Siglec15. Dr. Porter and colleagues will determine if B-ALL impairs EM, whether that is dependent on Siglec15 and if EM can be restored to improve the immune response to leukemia cells. Dr. Porter and team will demonstrate that impaired EM plays an important role in the cell's development.

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.

Relapsed/refractory pediatric acute myeloid leukemia (AML) is a challenging disease with poor survival. Combining two classes of drugs--thalidomide analogs (TAs) and menin inhibitors- may improve outcomes for patients with a particular genetic subtype of AML. Dr. Li has shown that TAs can affect the numbers and activity of a type of immune cell called regulatory T cells (Treg), which can prevent the immune system from recognizing and attacking leukemia cells. Treating pediatric AML patients with TAs and menin inhibitor, which is being tested in an upcoming clinical trial, may impair Treg activity and improve immune recognition and targeting of AML, potentially contributing to responses. Dr. Li will study the effects of combination therapy on models. Dr. Li's study will improve the efficacy and safety of new pediatric AML therapies by defining their effects on immune responses.

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

Children, adolescents, and young adults (AYA) diagnosed with sarcoma, often face long-term health challenges commonly seen among older adults who have never been diagnosed with cancer. This may be due to a phenomenon known as accelerated aging, where cancer and its treatment cause patients to age faster than they should. Dr. Robinson and colleagues will explore factors that may affect accelerated aging and the impact of accelerated aging on an individual's physical function and quality of life. Dr. Robinson and team will assess age acceleration among sarcoma patients and survivors, ages 12-25, and study its association with their demographics, lifestyle, disease, and treatment. In doing so, Dr. Robinson and colleagues will guide the development of interventions to improve the long-term health and well-being of pediatric and AYA sarcoma survivors.

This grant is named for Madison Richards Mighty Research Marauders, a St. Baldrick's Hero Fund. It was established to celebrate Madison's extraordinary courage and resilience. Madison survived a harrowing ordeal with Ewing sarcoma in her chest cavity. Her extended treatment required more than 140 nights in the hospital and included a month-long coma while she fought West Nile Virus. Through every challenge, she faced each days with remarkable grace and poise. When surgery and treatment were complete, she returned to high school, completed an 18-month mission for her church, and graduated from college. Madison is a true example of making it through the storm and living life to the fullest on the other side.

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.

The survival rates for children with cancer remains unacceptable and the treatments for childhood cancers continue to carry significant life-altering side effects as most treatments do not specifically recognize cancer cells and affect healthy cells. Dr. Guerra and colleagues are developing a therapy created from the white blood cells of a patient's own immune system, known as immunotherapy. These cells are engineered to target cancer cells by engaging a marker that is present on the surface of cancer cells but not present on healthy cells. When the engineered white blood cells engage this cancer-specific marker, the cells become activated and attack the cancer cells while sparing healthy cells. Additionally, this immunotherapy can be boosted with further engineering approaches to remain active in a patient for long periods of time, allowing for long-term killing of cancer cells which we predict will improve survival while reducing treatment-related side effects.

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

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.

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.

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.

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.

Neuroblastoma is one of the most common childhood cancers. Babies under 18 months often have tumors that can shrink on their own, while older children face more aggressive disease. This difference may be due to how the immune system works early in life. Infant T cells, the white blood cells that kill cancer, are more responsive and resist "exhaustion," a problem that limits current immunotherapies. Dr. Rowe and colleagues will study what makes infant T cells unique and use this knowledge to design improved, less toxic T-cell therapies for children with neuroblastoma and other hard-to-treat cancers. By discovering how early-life immunity naturally fights cancer, Dr. Rowe and colleagues will create safer treatments that cure more children and help survivors live long, healthy lives.

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.

Dr. Graves and colleagues will improve treatment for osteosarcoma, an aggressive bone cancer that frequently becomes resistant to chemotherapy. Cells that become resistant to chemotherapy often undergo adaptations to help them survive and recover. Dr. Graves will investigate how chemotherapy remodels iron usage and mitochondrial function to support survival in osteosarcoma cells. Early data suggest these cells become more dependent on energy production in the mitochondrial to survive. By impacting energy production, Dr. Graves and colleagues will test whether cancer cells become less resistant, grow more slowly, and will be less likely to spread. Dr. Graves will evaluate a new "multi-strike" treatment that delivers chemotherapy first, followed by carefully timed drugs that disrupt cancer cell metabolism before tumors can rebound. By identifying weaknesses in cells that survive chemotherapy and optimizing treatment timing, Dr. Graves and team will prevent tumor regrowth and improve outcomes in osteosarcoma.

Dr. Ruff and colleagues will develop a targeted medical therapy for adamantinomatous craniopharyngioma, a brain tumor that affects children and causes lifelong vision loss, hormone problems, and cognitive impairment in the majority of survivors. Currently, the only treatments are surgery and radiation, which often cause irreversible damage to the developing brain, and despite this the tumor frequently comes back requiring repeated interventions. Combining two existing FDA-approved medications to shrink these tumors dramatically, Dr. Ruff and colleagues will study how likely these medications are to work in patients with this tumor. By analyzing tumor samples for the medication target and patient responses, Dr. Ruff and team will design a clinical trial that could transform care for children with this disease.