Grants Search Results

The shape and function of bone, fat, muscle, and other connective tissues evolve through a carefully orchestrated process that leads mesenchymal stem cells (MSCs) to progressively differentiate into more lineage-restricted tissue-specific phenotypes. As this occurs, MSCs must interpret their surrounding extracellular milieu. When everything works correctly, normal mesenchymal tissues emerge. When disrupted, as tragically occurs with Ewing sarcoma (ES), the aberrant fusion protein (FP) acts as powerful transcription-factor that corrupts the epigenetic program and locks ES in an undifferentiated state unable to interpret or respond to the biophysical cues present in the tumor microenvironment. Attempts to understand the FP’s effect upon tumor-ECM interactions within monolayer culture systems that lack a native tumor microenvironment has contributed, not unexpectedly, to spurious results that overestimate the clinical effectiveness of chemotherapy. To close this gap, Dr. Ludwig's multi-disciplinary team is using an innovative 3D tissue engineered model, pioneered by his laboratory, to assess next-generation EWS-FLI1-targeted therapies within a physiological microenvironment that cannot readily be studied in vivo. This project will shed new light on ES biology and promises to improve the ability to co-target the FP and other proteins that maintain the aggressive, poorly differentiated state of ES.

This grant is generously supported by the Shohet Family Fund for Ewing Sarcoma Research. Noah was diagnosed with Ewing sarcoma in his freshman year in college. After limb salvage surgery and chemotherapy, he was able to return to school. Two years later, Noah relapsed. This Hero Fund honors his courageous fight and hopes to raise funds for Ewing sarcoma research.

We can now manipulate the immune system with remarkable precision and efficacy to fight certain cancers. However, tumors adapt to reduce immunotherapy efficacy. This is true for solid tumors including osteosarcoma. Therapy-refractory metastatic osteosarcoma represents a pressing unmet need, as the outcome has not improved for over 3 decades. This multi-institutional collaborative proposal explores tumor-extrinsic pathways by which pulmonary metastatic osteosarcoma evade immunity. Dr. Huang’s team is focusing on key molecules responsible for such evasion, against which existing or emerging therapeutic agents are available currently or in the very near future. Therefore, uncovering these pathways could realistically offer multiple new clinical trials for pediatric and AYA metastatic osteosarcoma in the next 3 years. This Osteosarcoma Collaborative St. Baldrick's Grant to Cure Osteosarcoma is funded through the generosity of the Osteosarcoma Collaborative.

Despite the use of multimodal treatments and the implementation of several clinical trials worldwide, pediatric cancers survival rate has come to a standstill for the last decade. Moreover, intensive therapies are not devoid of long-term side effects, notably increasing lifetime risk for secondary malignancies. The duty of the pediatric oncologist is to propose the most adequate treatment to cure pediatric patients with the best quality of life for a long time. Therefore, understanding the biological underpinnings of pediatric malignancies is crucial to develop new therapeutic paths adapted to the specificities of a young organism. A major pitfall is the lack of adequate experimental models. To overcome this problem, Dr. Broutier is developing patient-derived 3D-organoid models (mini-tumor growing in a dish) of pediatric cancers. Beside their broad interest for research community, she will use them to identify mechanisms involved in cell death resistance in pediatric cancers, as a key step towards development of new targeted therapies adapted to children and adolescents.

Nearly half of all children diagnosed with Acute Myeloid Leukemia (AML) will suffer a relapse after initially successful treatment. Whereas therapy efficiently clears the bloodstream of leukemia cells, frequent evidence of residual drug resistant disease points to a leukemia protective role of the bone marrow microenvironment. The mechanism by which the bone marrow acquires these protective abilities is not clear. Dr. Kurre recently observed that so called stroma cells, that provide bone marrow structure and support are functionally altered. Pilot studies conducted by Dr. Kurre also identified a new mechanism by which AML changes these stroma cells. In this project Dr. Kurre is studying pediatric AML samples to understand how the altered stroma protects leukemia cells from the effect of drugs commonly used to treat children with AML. The long term goal is to develop treatment approaches that reduce the burden of relapse, by maintaining initial remissions in children with AML, and without further escalating drug toxicity. Awarded at Oregon Health and Science University, and transferred to The Children's Hospital of Philadelphia.

Based on progress to date, Dr. Osborn was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. Abnormal growth of B-cells can result in leukemia, and a cutting-edge treatment option is immunotherapy with T-cells. T-cells can be engineered to express a chimeric antigen receptor (CAR) that is a 'seek and destroy' molecule for the CD19 protein on B-cells. CAR T-cells are the first FDA approved gene therapy and some stunning therapeutic responses have been observed. However, the T-cell activity can be so robust that they cause a massive cytokine storm that can be lethal. Furthermore, normal and cancerous B-cells express the CD19 protein targeted by the CAR, so normal B-cell loss occurs resulting in an impaired immune system. These side effects represent a significant hurdle in the safe and effective treatment of B-cell leukemia. To address this, Dr. Osborn, will express the CAR in a specialized subset of cells called T-regulatory (Treg) cells. Tregs have the same potent killing ability as T-cells but accomplish it without healthy tissue collateral damage. Additionally, he will engineer functional B-cells that are invisible to the CAR. This will allow for normal B-cell numbers and an intact immune system. Dr. Osborn will conduct these studies that are structured to resolve an unmet need, are highly novel, and are poised to make an immediate impact on childhood leukemia. 

The 2022 portion of this grant is named for the Rays of Hope Hero Fund which honors the memory of Rayanna Marrero. She was a happy 3-year-old when she was diagnosed with Acute Lymphoblastic Leukemia (ALL). She successfully battled ALL, but a treatment induced secondary cancer claimed her life at age eight. Rayanna had an amazing attitude and loved life. She, like so many kids facing childhood cancer, did not allow it to define who she was. This Hero Fund aspires to give hope to kids fighting cancer through research.

A portion of this grant was funded by and named for the Mighty Mimi Hero Fund. Mimi Enyon was diagnosed with acute lymphoblastic leukemia at the age of 3. Her courage in the fight was unparalleled and she became “Mighty Mimi” to all those she inspired on her way to remission. This fund was established to share Mimi’s cancer journey in an effort to raise awareness and funding for childhood cancer research for kids like her.

A portion of this grant is generously supported by the Stanley Kuzmickas Feeney Fund for Pediatric Cancer Research. It was Christmas 2015 when Stanley was diagnosed with acute lymphoblastic leukemia at 13 months old. He courageously endured treatments for 3½ years. Today, he is in remission and eagerly started school in fall 2019. In his honor, Stanley’s family has organized a head-shaving event each year since July 2016 called “StoshyStrong." With the funds raised, the Feeney family created this Hero Fund to support research in new discoveries, genomics and other biological therapies for the treatment of ALL. Their goal is to one day see personalized treatments for every child.

Neuroblastoma is a cancer formed in certain types of nerve tissue and is the most common pediatric solid tumor outside of the brain. It is the leading cause of cancer-related death in children under five years old. Those patients who do survive often develop long-term side effects from intensive chemotherapy and radiation therapy. Thus, we need to develop better, safer alternative therapies for neuroblastoma. Dr. Cripe is currently studying the use of genetically modified herpes viruses. These viruses, which include the recently FDA-approved herpes virus T-VEC, can selectively infect and kill cancer cells without harming normal cells. In addition, these viruses are also able to enhance the patient's immune response against the cancer cells, potentially leading to a systemic and long-lasting protective immunity against cancer dissemination and recurrence. In the course of his studies, Dr. Cripe found that tumors infected with virus induce a counter measure by attracting cells that suppress immunity. In this study, he will test if he can improve therapy by interfering with that counter measure. If successful, these results may lead to a novel clinical trial for neuroblastoma patients.

Current cancer therapy is very toxic and does not always work. We have developed a way to deliver much more drug to the tumor, and much less to the patient, by packaging the drug in properly designed nanomedicines. These delivery systems take advantage of the fact that most aggressive tumors have leaky blood vessels, so our nanomedicines can pass through into the tumor, but they bypass most normal tissues. Using these formulations, we can deliver 10-100 times as much drug to the tumor, so we can use less total drug and still get better results. In addition, Dr. Brodeur is using a novel drug called SN22. Although SN22 is related to a commonly used chemotherapy agent called irinotecan, it is an active drug, and unlike irinotecan it does not have to be activated by the liver. It is not only much more potent but also harder for the tumor cells to get rid of. These features make SN22 much more therapeutically effective. The carrier Dr. Brodeur is using to make this nanomedicine can deliver four molecules of SN22 within each “packet” that enters the tumor. Because he can use less total drug, and because the nanomedicine can circulate for a long time with the drug attached, there is much less exposure to the rest of the body, so side effects are dramatically reduced. As the recipient of the Invictus Fund St. Baldrick's Research Grant, Dr. Brodeur's goal is to develop more effective but less toxic therapy to treat children with cancer, and he can accomplish that goal with this approach using nanomedicine-based drug delivery. The nanomedicines he is developing should be effective against many different solid tumors in children or adults and he hopes to bring them forward to Phase 1 clinical trials.

This grant is funded by and named for the Invictus Fund, a St. Baldrick's Hero Fund created in memory of Holden Gilkinson and honors his unconquerable spirit in his battle with bilateral Wilms tumor as personified in the poem “Invictus” by William Ernest Henley. His family hopes to fund cures and treatments to mitigate side and late effects of childhood cancer.

Neuroblastoma is a cancer of the nervous system that causes aggressive disease in infants and young children, and the overall survival rate of high-risk (stage IV) patients is low. Ornithine decarboxylase (ODC) is a validated target in several cancers and we advanced the ODC inhibitor DFMO into neuroblastoma clinical studies. While promising, large quantities of DFMO are needed for patient treatments because about 80% of the drug is released into the urine. To improve the retention of DFMO in the blood, this study explores the combination of DFMO with an FDA-approved adjuvant. We expect that DFMO in the presence of this adjuvant will (a) increase the DFMO concentration in the blood and (b) induce more potent anti-tumor effects in neuroblastoma tumor-bearing mice. Since both DFMO and the adjuvant are FDA-approved drugs, this new regimen could rapidly advance to neuroblastoma clinical studies.

Phthalates are chemicals added to many products that we use every day, including some common medications. Phthalates interfere with hormone systems in our bodies, which might cause cancer. Dr. Ahern wants to know if phthalate exposure while in the womb or during childhood increases the risk of childhood cancer. It would usually be time-consuming and expensive to answer this question scientifically. However, Dr. Ahern's team has developed a way to measure phthalate exposure using electronic pharmacy records that is both fast and inexpensive. This technique works because phthalate exposure from medications dwarfs exposure from other products. He will use this technique on existing pharmacy and cancer data from the entire population of Denmark. Dr. Ahern will measure phthalate exposure in pregnant women and in their children, and calculate whether that exposure increases a child's chances of developing cancer. If he finds that it does, we could prevent childhood cancer cases by limiting the amount of phthalates used in consumer products.

Osteosarcoma is the most common primary bone tumor in childhood. The survival rate remains dismal, mainly due to ineffective therapeutic approaches for the relapsed/metastatic patients. One major obstacle of treating osteosarcoma is lack of suitable preclinical models. Dr. He's studies have established the first cultured osteosarcoma tissue model (an organoid). Dr. He aims to establish the first biobank of osteosarcoma organoids from patients as an open resource for the field, and utilize this organoid biobank to evaluate a novel class of therapeutics targeting key signaling pathways in osteosarcoma cells. This study will provide a powerful platform for predicting clinical treatment responses and developing new therapeutics for treating osteosarcoma.

Cancer cells rely on specific nutrients for growth and survival, rendering nutrient restriction as a potential therapeutic strategy. Along this line, acute lymphoblastic leukemia (ALL) cells have been found to be dependent on exogenous supply of asparagine, a nonessential amino acid, for protein synthesis. As a result, depletion of asparagine in the blood stream by L-asparaginase, a chemo-agent, has been successfully used to treat pediatric ALL for 40 years. However, ALL patients can develop resistance to the continuous application of this chemo-agent. Dr. Zhang is determining how ALL cells become resistant to L-asparaginase treatment, and therefore to provide experimental evidence of novel therapeutic targets that can potentially improve the outcome in pediatric ALL patients.

Sarcomas are tumors of the bone and soft tissues that comprise up to 20% of cancer diagnoses in children. Despite dismal outcomes for patients with recurrent or metastatic disease, treatment regimens have remained largely unchanged for decades – intense non-specific chemotherapy combined with surgery or radiation. Dr. Tulpule studies Ewing’s sarcoma (ES), a bone tumor caused by a unique genetic change that creates a tumor-specific protein EWS-FLI1. To date, no drug has been identified to directly block the cancer causing EWS-FLI1 protein. His research takes a different approach to combating ES by asking a fundamental question: can we identify a targetable weakness in ES tumors that is caused by the EWS-FLI1 protein? Using a cutting-edge screening technology called CRISPR interference, Dr. Tulpule's team identified a specific vulnerability in ES cells’ capacity to repair damage to their DNA. Normal cells have many backup systems in place to repair DNA damage, but they have shown that EWS-FLI1 causes ES cells to become overly reliant on a single pathway, known as homologous recombination (HR) repair, such that blocking HR is an effective and specific way to kill ES. Dr. Tulpule is building a detailed understanding of why ES cells are so vulnerable to HR pathway blockade and then applying that knowledge towards developing less toxic and more effective treatments for ES patients.

Based on progress to date, Dr. Peltier was awarded a new grant in 2020 to fund an additional year of this Fellow award. Bone marrow transplantation (BMT) is required to cure many childhood cancers. However, bone marrow transplantation is often complicated by severe and often fatal side effects. Both the beneficial anti-cancer effects and harmful side effects of bone marrow transplantation are due in part to the new immune system that the patient receives. Unfortunately, we do not know how to precisely fine tune this new immune system to make BMT safer for more children. As the Hope for Harper St. Baldrick's Fellow, Dr. Peltier seeks to further understand in his work how a component of this new immune system is controlled by a recently identified class of genes called non-coding RNAs (ncRNA). These ncRNA genes do not make proteins like classic genes, but instead regulate the production and function of proteins made by classical genes. His early data shows that unique ncRNA genes from multiple classes of ncRNAs are turned on and off following BMT. However, it is not known if or how these unique ncRNA genes influence the new immune system after BMT. Dr. Peltier seeks to further understand the function of these ncRNAs following BMT, which may suggest ways of developing medicines to improve BMT.

This grant is named for and generously supported by the Hope from Harper Fund created to honor Harper Wehneman who was diagnosed with Wilms tumor just before her 8th birthday. She fought valiantly throughout her cancer journey and is remembered for inspiring people to choose joy no matter the circumstance. This fund continues her legacy by giving hope to kids fighting cancer through research for stem cell transplant survival.

Based on progress to date, Dr. Ch'ng was awarded a new grant in 2020 to fund an additional year of this Fellow award. Epstein-Barr virus (EBV) is a common viral infection that in the vast majority of people causes only minor or no illness. However, in some situations it can play a role in the development of certain forms of cancer, such as lymphoma. One way that it might contribute to the development of cancer is by affecting the way that cells use energy because viruses and cancers both require increased energy to support rapid growth. By studying how EBV changes the way that cells use energy, Dr. Ch'ng hopes to learn whether changes in cell energy use are a factor in the development of cancers associated with EBV and whether these changes can be targeted to treat these forms of cancer.

Osteosarcoma is a cancer of bone that typically affects teenagers and young adults. Tumor spread (or metastasis) to the lungs is common, and up to 40% of patients with osteosarcoma will eventually experience a cancer recurrence (or relapse). Unfortunately, no therapies have shown benefit following relapse and these patients have a very poor prognosis. The ability of cancer to control and hide from the body’s immune system is important for tumor growth and metastasis, so preventing these functions is an important treatment strategy. Recent work, including a canine osteosarcoma trial, has shown that currently available medications may work together to block some of the effects that cancer has on the immune system, reducing tumor growth and the ability to spread. Dr. Faulk will conduct a clinical trial which will combine these drugs (losartan and sunitinib) in children and young adults with relapsed osteosarcoma to test the safety of the new combination, see how the drugs are broken down by the body, and determine how the drugs affect the immune system and the growth of the tumor.

Based on progress to date, Dr. Dharia was awarded a new grant in 2020 to fund an additional year of this Fellow award. Despite progress made in the treatment of pediatric cancers, several childhood cancers, such as high-risk neuroblastoma, Ewing sarcoma and rhabdomyosarcoma, continue to have poor survival rates. It is critical that we identify new therapies for these cancers, especially now that we are learning how cancers are driven by specific changes in proteins that bind DNA and control transcription. Researchers are beginning to identify potential vulnerabilities in cancers by systematically deleting almost every single gene in a cancer cell, and describing in greater detail the mutations and other events that occur in pediatric cancers. As the Julia's Legacy of Hope St. Baldrick's Fellow, Dr. Dharia and his team are integrating data from such approaches to discover specific vulnerabilities in high-risk neuroblastoma, Ewing sarcoma and rhabdomyosarcoma. Different types of cancer cells require different instructions or programs to survive, and Dr. Dharia proposes the identification of these programs will lead to new targets to treat these cancers. By identifying, validating and characterizing new targets for treatment of these childhood cancers, Dr. Dharia hopes to discover new therapies for cancer care. This research will take advantage of drugs that are already available and ideally identify completely new ways to treat these cancers.

This grant is named for Julia's Legacy of Hope, a Hero Fund that honors her positive, courageous spirit and carries out her last wish: "no child should have to go through what I have experienced". Diagnosed at 16 with Ewing sarcoma, Julia fought cancer and survived only to be stricken by a secondary cancer as a result of treatment. Her family hopes to raise awareness and funds for research especially for Adolescent and Young Adult (AYA) patients.

Pediatric undifferentiated sarcomas are highly aggressive cancers that typically affect soft tissues of young children. Due to their uncertain classification and lack of molecular signature there are no standard criteria for diagnosis or treatment. With the Alan's Sarcoma Research Fund St. Baldrick's Research Grant, Dr. Antonescu is applying state of the art genomic methods to provide a detailed genetic characterization in these orphan cancers and investigating driving chromosomal translocations or mutations involved in their growth. These results will establish an objective classification of these tumors based on their genetic abnormalities and will provide potential therapeutic targets for further novel therapies. Furthermore these findings will inform the generation of faithful models for studying sarcoma formation and new drug development.

This grant is funded by and named for the Alan's Sarcoma Research Fund, a St. Baldrick's Hero Fund. Alan Sanders was diagnosed with a rare sarcoma in his hip at 17 months. He had an indomitable spirit and throughout his 4 ½ year battle with cancer, he was joyful, upbeat and pressed on courageously in spite of surgery and treatments. Today his family and friends carry on his legacy and his rallying cry, “Fight’s on!” in the battle against childhood cancer by funding sarcoma research.

The lives of children surviving cancer are cut short by life-threatening infections. Most pathogens causing these infections come from the gut. Healthy children have good bacteria in their gut that protect them from pathogens. Chemotherapy and antibiotics harm good bacteria in the gut that protect children from pathogens. Without good bacteria, pathogens increase in the gut. These pathogens can get into the bloodstream and cause serious infections. Prior studies have repeatedly shown that replacing healthy stool with good bacteria in the gut is the best treatment and prevention of gut infections. Dr. Andersen's team is developing a new test that detects the good bacteria and pathogens in the gut using a stool sample. This new test will allow earlier identification of children with cancer at the greatest risk for a serious infection and the children most likely to benefit from replacing healthy stool with good bacteria back in their gut. They believe that replacing good bacteria in the gut can prevent serious infections from pathogens, including those with limited antibiotic treatment options. This new test will also identify the specific good bacteria in the gut that prevent infection for developing new probiotics to prevent serious infections in children with cancer.

People always say we need to outsmart cancer to beat it. As the Hope with Hazel St. Baldrick's Scholar, Dr. DuPage is not sure we will ever be able to do this with simple chemicals or radiation beams. Not only are these strategies rarely specific for the cancer cells alone, often leading to severe side effects that can be lifelong, but cancers always find a way around these single agents and "relapse." What if we could use a "living drug" to treat cancer? A drug that was as wiley and adaptable as the cancer itself and would last for a lifetime? A smart drug! Our own immune systems are capable of fighting our own cancers with extreme precision if we can train them to do it. This research is focused on understanding how cells of our immune system interact with tumor cells and how we can train our own immune cells to fight our own cancers. It is called cancer immunotherapy, and for children with cancer, Dr. Dupage thinks there are no better patients because their young and healthy immune systems are perfectly suited to be trained to fight cancer, removing the need for procedures that can manifest dangerous side effects in adulthood, and safely protecting them for life.

This grant is named for the Hope with Hazel Fund in honor of Hazel Hammersley who was diagnosed with Stage III neuroblastoma at age 2. She endured treatments, surgeries and two relapses with an amazing ability to push through and live life to its fullest. She loved her family and her happy place was with them. Through Hazel, her family learned that no one can fight pediatric cancer alone. This fund remembers her love of life and is dedicated to raising awareness and funds for research to protect kids with cancer who are still in the fight.

Today, over 80% of children diagnosed with cancer in high income countries like the United States will survive. Considered a miracle of modern science, these gains are unfortunately not reflective of outcomes for the 90% of children with cancer who live in low- and middle-income countries (LMIC). Yet, as many LMIC continue their epidemiological transition away from overwhelming infectious disease to a greater non-communicable disease burden, cancer care has recently become a major global focus. As policy-makers now begin the cancer control and prioritization planning process to meet this challenge, estimates of global and national cancer-related disease burden are a critical piece of data required when making decisions. However, current efforts meant to generate global pediatric cancer burden data such as incidence, mortality and long-term morbidity measures are not ideally suited for this purpose as they are optimized to measure adult cancer burden and do not incorporate key pediatric-specific data sources. Instead, a pediatric cancer specific analysis is needed since children are sufficiently different from adult cancers such that new methods, which account for small numbers of cases, the lack of etiologic risk factors, histology-based classification codes, and the long-term effects of treatment, are required. As the Friends for Hope Fund St. Baldrick's Scholar, Dr. Bhakta will address this critical gap by producing comprehensive pediatric cancer-related burden estimates using the most current data sources and rigorous statistical estimation methods. It is anticipated the results of this study (to be published and made publicly available) will provide global stakeholders and policymakers key outcomes data to cure more children with cancer globally.

This grant is named for the Friends for Hope Fund created to honor Morgan Loudon and celebrates her strength and determination as a cancer survivor. Diagnosed when she was 9 with a rhabdoid tumor, today she has no evidence of disease. Through this fund, Morgan's family and friends hope to 'battle on' in the search for cures and better treatments.