It is known that children with cancer have higher rates of hospitalization, ICU admission, and death than children without cancer and COVID-19. Children with cancer and COVID-19 also frequently have changes in their chemotherapy. Yet, critical data is lacking regarding COVID-19 in children with cancer and guidelines about how to manage these vulnerable children. Dr. Johnston and collegaues will leverage the national registry of children with cancer and COVID with data on >2,400 children from >100 institutions to examine (1) how the clinical course of children with cancer and COVID-19 compares to earlier in the pandemic, (2) how the clinical course of COVID-19 in children with cancer is impacted by vaccination and antiviral therapy, and (3) physician and healthcare systems factors that influence COVID-19 management. Dr. Johnston will use that information, literature review, and expert discussion to inform an expert panel tasked with developing guidelines for management of COVID-19 in children with cancer.

Acute myeloid leukemia (AML) is the second most common type of leukemia in children. Despite treatment advancements, over 30% of children with AML cannot be cured. In AML cell populations, the leukemia stem cells (LSCs) make up a small part of the total, but are specially important: they provide a steady supply of new AML cells and are unfortunately very resistant to killing with drugs. Dr. Sui and colleagues believe that if they are able to kill the LSCs, they could cure patients with AML. Dr. Su has found that an enzyme called METTL1 is important in allowing LSCs to safely stay anchored in the bone marrow and identified a drug that inhibits METTL1 and eliminates LSCs. Dr. Su's study explores why METTL1 is important for LSCs and investigates how Dr. Su and team could best use their in-house developed METTL1 inhibitor to treat childhood AML using model systems. If successful, this research could pave the way for a clinical trial, offering hope for improved outcomes for childhood AML patients.

This grant is generously supported by Double Deckers Destroy AML, a St. Baldrick's Hero Fund. Joel and Seth were not only identical twins but best friends. In an ironic twist of fate, both boys were diagnosed with Acute Myeloid Leukemia just three months apart. With the overlapping diagnoses and treatments, the family was separated for months at a time and looked forward to days when they could be together at home. Joel and Seth both received bone marrow transplants and endured complications from the procedures. Sadly, both boys relapsed. Surrounded by their loving family, Joel died in November 2017 at the age of three, followed by Seth in May, 2019 when he was four years old. The twins were named as 2020 Ambassadors for St. Baldrick's so their story can continue to inspire many. The Double Deckers Destroy AML Hero Fund was established because the Decker family strongly believes more research is needed for AML, especially when the disease has relapsed. They want to support research so other families won’t have to say goodbye too soon.

Acute kidney injury (AKI) commonly occurs during therapy for acute lymphoblastic leukemia (ALL). Small studies in pediatric ALL have suggested that AKI increases the chance of dying or the treatment not working. AKI may also lead to permanent chronic kidney disease (CKD) in survivors. This has never been investigated in a large population of children with ALL. This project will use data from the multicenter Leukemia Electronic Abstraction of Records Network to investigate how different types of AKI impact survival from ALL and the development of CKD. Dr. Hsiao and colleagues will enroll children who have completed ALL therapy into a study to assess markers of kidney function over the subsequent year. This study will be critical to inform recommendations for how doctors screen for kidney-related problems in childhood ALL survivors. This is only a first step; once completed, Dr. Hsiao and team can then expand these efforts to understand kidney damage from treatments for other types of cancer too.

This grant is named for To-morrow's Research Fund, a Hero Fund created to honor Becky Morrow who is a childhood cancer survivor. Becky was diagnosed with acute lymphoblastic leukemia when she was 12 and endured grueling treatments and its side effects. Today she is cancer free, a wife and a mom but suffers late effects. This fund supports survivorship research for safer treatments that help kids not only survive but thrive.

Medulloblastoma (MB) is an aggressive childhood brain cancer that is fatal in 40% of patients. MB shows abnormal activation of growth pathways in tumor cells which help them to grow. Dr. Ganesan's studies show that there are T cells (immune cells) within MB and they have potential to kill tumor cells. However, immunotherapy that boosts the activity of these T cells have not been successful and it is not known why. The goal of this project is to understand why immunotherapy has not worked in MB and whether immunosuppressive myeloid cells contribute to this restraint. Dr. Ganesan and colleagues will also study if combined treatment that inhibits the growth pathways (targeted therapy) and stimulates the T cells/immune system (immunotherapy) may together lead to greater tumor killing in MB mouse models. To test if combined therapy would work in humans, Dr. Ganesan will coculture a 3D version of patient’s brain tumor with their own T cells expanded from their tumor. If effective, these studies may lead to new treatments for MB.

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.

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.

Allogeneic cell therapy is a new approach to cancer treatment that harnesses living cells from healthy donors to fight tumors. To do so, immune cells are isolated from blood and incubated outside the body to expand subsets capable of killing cancer. Dr. Jonus and colleagues have shown that gamma delta (gd) T cells expanded from healthy adults help to eradicate neuroblastoma grown in models. Based on this,Dr. Jonus and team are performing a first-in-child clinical trial of gd T cells for patients with neuroblastoma. Going forward, Dr. Jonus's findings show an opportunity to make gd T cell therapy more effective by expanding a new type of gd T cell, Vd1, with unique properties that should improve both the cell therapy's fitness and its ability to infiltrate into solid tumors. In parallel for a potent second-generation therapy, Dr. Jonus will engineer Vd1 gd T cells to 1) express receptors that help them better recognize neuroblastoma and 2) evade immune recognition so that the therapy is not killed after being infused into a patient.

The first year of this grant is funded by and named for the Oliver Wells Fund for Neuroblastoma, a St. Baldrick's Hero Fund. From the moment he was born, Ollie was the center of the Wells family with a contagious smile and a sparkle in his eyes. As the youngest child, it was devastating when they learned the 15 year old toddler had cancer. Oliver was diagnosed with high risk neuroblastoma and spent the next 13 months bravely enduring chemotherapy and radiation, more than a dozen surgeries and a bone marrow transplant. But Ollie persevered and smiled through it all. It was an unfair fight from the beginning and in July 2018, Ollie passed away. The Oliver Wells Fund for Neuroblastoma was established in his memory to raise funds to find cures and give hope to other kids facing the same fight. In this way, the Wells family intends to share Oliver’s joy for life and use his story to help find a cure.

Even after being cured, childhood cancer survivors face challenges to living a healthy life, and one major challenge is heart disease. Heart health is closely linked to healthy eating, but many survivors cannot eat as healthily as they want because they don't have access to, or can't afford, healthy foods ("food insecurity"). Dr. Aziz-Bose will enroll survivors in this study to ask what they are eating, and understand whether they experience food insecurity and other conditions that put heart health at risk. Survivors will also be interviewed for their ideas about how to support healthy eating, including the best ways to directly give families healthy foods, an approach called "food is medicine." Using this information, Dr. Aziz-Bose will fine-tune a "food is medicine" intervention that she developed, and test it on a larger scale to see its impact on food insecurity and heart health. The goal being to understand and tackle barriers to healthy eating so all survivors can have the best health possible.

Despite remarkable improvements in treatment for children with some types of cancer, pediatric brain tumors remain an area that desperately require more effective and low toxic therapy solutions. Dr. Jun Qi has formed a multi-disciplinary team to identify novel targets for pediatric brain tumors and develop new strategies to suppress the targets for patient treatment. Using a chemical strategy, Dr. Qi and his team aim to disrupt the functions of these targets to effectively inhibit brain tumor cell growth and block tumor progression in the models that resemble the real disease. The study focuses on improving on-target effect and, more importantly, on getting these potential drug candidates into the brain. The proposed study will translate from bench to bedside for patient care and result in a novel therapeutic strategy with significant improvements in survival and reduced morbidity for pediatric brain tumor patients to fulfill the mission of St. Baldrick’s Foundation.

Survivors of pediatric brain tumors have a high risk of medical problems that can negatively affect the quality of their lives. Particularly concerning are effects on brain development, including learning and emotional well-being, and metabolism, which can lead to obesity and muscle loss. There is an urgent need for tools that can better predict which children are most at risk so that they can be offered treatments to prevent these problems. Dr. Kann's and colleagues have developed medical imaging tools that use artificial intelligence on routine brain scans to track and predict 1) muscle weakness and malnutrition, and 2) brain development in children. Dr. Kahn and team will test these tools in large datasets from hospitals and clinical trials of pediatric brain tumor patients and survivors to predict the risk of these negative effects in each patient. The tools developed may be used in clinical trials to improve quality-of-life for childhood brain tumor survivors.

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.

Diffuse midline glioma (DMG), previously known as diffuse intrinsic pontine glioma (DIPG), is a deadly childhood tumor with no effective treatments. Dr. Li's project seeks to understand the genetic and epigenetic dysregulation of DMGs. Through cutting-edge single-cell analyses and advanced AI models, researchers aim to map the tumor's epigenetic landscape, identify key regulatory elements, and predict the function of risk mutations. This knowledge could pave the way for new targeted therapies and improve DMG outcomes.

This grant is generously supported by the #Joe Strong 71 Hero Fund. The fund was established in memory of Joe Purdue. Joe was a talented football player and cherished member of his class. He was diagnosed with DIPG shortly after graduating from high school, cutting short his plans to attend college. He is remembered for determination while he faced his difficult battle with the most lethal form of brain cancer. The #Joe Strong 71 Fund carries on Joe's legacy by funding research for DIPG and DMG.

Hepatoblastoma is the most common liver tumor diagnosed in early childhood, and new therapies are urgently needed to improve survival and reduce treatment related morbidity. Immunotherapy is a type of cancer treatment that harnesses the body's own immune system to target and attack cancer cells. While some immunotherapies have been very successful against certain tumor types in adult patients, they have been largely unsuccessful in treating pediatric tumors. This demonstrates how little we know about how the pediatric immune system responds to tumors. Using samples and models of hepatoblastoma, Dr. Cabric's research aims to identify the key immune cells involved in recognizing and responding to hepatoblastoma. Identifying the key immune cells involved in tumor immunity, and mechanisms that allow tumors to escape detection and deletion by the immune system, will allow us to find novel targets for future immunotherapies that work in children.

Whilst it is well known that damage to our DNA can cause cancer, is is still not fully understand what causes such DNA damage in many childhood cancers. Dr. Wang and colleagues recently made a breakthrough by discovering that our own body produces a natural toxin called formaldehyde that causes DNA damage and an aggressive blood cancer in children. This was a shocking discovery as it had previously been thought that formaldehyde mainly came from industrial chemicals found in factories. Dr. Wang's overall aim in this research proposal is to unravel exactly where formaldehyde toxin is made in our body. This knowledge can help to identify children at risk of developing blood cancers, and to develop strategies to modulate the production of formaldehyde as novel therapies against blood cancers.

The first year of this grant is is generously supported by RowOn 4 A Cure, a St. Baldrick's Hero Fund. Rowan was a happy, spunky, funny, smart, and smiley little girl. With that same tenacity, she faced her cancer diagnosis of a rare form of acute myeloid leukemia when she was three. Despite intense chemotherapy and radiation and a successful cord blood transfusion, Rowan relapsed after a brief remission. The family relocated in search of another treatment option but before one could be found, Rowan sadly passed away. RowOn 4 A Cure was established to honor Rowan and continue her fight against AML by raising awareness and funds for research to find better options for treatment of relapsed AML and ultimately, a cure for the disease. Her family remembers Rowan’s perseverance during tough treatment days and intend to make an impact as they “Row On” to find a cure.

In some types of cancer that affect children and teenagers, there are special proteins called 'fusion oncoproteins' that play a big role. These proteins are made when a gene called MLLT10 gets mixed up with other genes. These cancers are very dangerous and don't respond well to treatments available now. Dr. Lui and colleagues research is focused on the most prevalent MLLT10 fusion oncoproteins, common in a type of cancer called T-cell acute lymphoblastic leukemia (T-ALL) in kids and young adults. Findings show that this fusion protein makes groups of biomolecules called 'condensates,' which can mess up how cells read and use their genetic instructions. Dr. Lui believes that by studying these MLLT10 fusion oncoproteins in detail, they may learn how they change cells and find ways to stop them. Dr. Lui also believes if they can figure out how MLLT10 fusion oncoproteins work, it may also help to understand other similar fusion proteins. That knowledge could help develop better treatments for these kinds of cancer.

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.

Acute myeloid leukemia (AML) is a blood cancer that affects children. AML treatment involves intensive chemotherapy that requires over 140 days in the hospital. This places immense financial burden on families including medical bills, transportation costs, childcare, and missed days from work. This burden and resulting distress are called financial toxicity. Dr. Zheng's research is focused on measuring financial toxicity and trying to figure out what can be done about it. One important idea to consider is that many parents quit their jobs or reduce their hours to care for their child. Dr. Zheng plans to use surveys and interviews to gain a clearer picture of how work disruptions develop over AML treatment and lead to financial toxicity. Dr. Zheng wants to identify what work arrangements and policies could offer the most support. Ultimately, it could lead to advocating for more flexible work schedules, remote work options, or other accommodations that could make a real difference for these families.

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.

The ultimate goal of this project is to define the safest, most effective therapies for children and young adults with Langerhans cell histiocytosis (LCH), which aligns with St. Baldrick's mission to find cures for childhood cancers and give survivors long and healthy lives. LCH is a blood cancer most common in children that creates destructive inflammatory lesions that can be fatal. LCH is caused by mutations activating the MAPK growth pathway in developing blood cells. Current front-line therapy fails to cure over 50% of patients with disseminated disease, and safe and effective options for subsequent therapy is not known. High-dose chemotherapy can be effective, but is toxic. MAPK inhibitor therapy alone does not appear to be durable based on early trials. Dr. Allen and colleagues hypothesize that MAPK inhibition will make cells more sensitive to chemotherapy. Dr. Allen will therefore test safety and efficacy of a new approach of combining chemotherapy with targeted MAPK inhibitor therapy.

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer with more than 3000 children/adolescents under the age of 20 diagnosed with ALL each year in USA. ALL affects a type of white blood cells called lymphocytes that help the body fight infection and disease. ALL can be broadly divided into either B-ALL or T-ALL. B-ALL affects a type of lymphocytes called B-lymphocytes whereas T-ALL affects T lymphocytes. Historically children with T-ALL have worse prognosis than B-ALL. B-ALL also have better therapeutic options whereas children with T-ALL are limited to therapies with well documented long-term negative effects like chemotherapy, radiation therapy. In this proposal, Dr. Thansapani and colleagues aim to evaluate a new therapeutic approach of nutrient deprivation to treat T-ALL grounded on their strong preliminary finding that T-ALL cells need high levels of the nutrient valine for their growth and survival. Dr. Thandapani's project investigates different avenues exploiting this vulnerability.

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”.