Grants Search Results

Rhabdomyosarcoma (RMS) is a rare and devastating cancer of childhood. Identifying and characterizing novel genes essential for RMS cancer growth can help improve our understanding of RMS disease process. Novel genes identified can also serve as potential therapeutic drug targets for treating RMS patients. BCOR is among the most frequently mutated genes in RMS. However, the role of BCOR in promoting cancer growth and disease progression remains unexplored. As the recipient of the Glen Parker Bayne Hero Fund St. Baldrick's Research Grant, Dr. Chen is working to characterize the biological function of BCOR in RMS. Completion of the study will not only provide new insights into the role of BCOR in the disease process of RMS, but also therapeutic rationale for targeting BCOR in improving survival outcomes of RMS patients.

This grant is named for the Glen Parker Bayne Hero Fund which was established to honor this little boy's courageous battle with rhabdomyosarcoma and celebrate his survivorship. Glen was diagnosed when he was almost 2 and endured a year of intensive treatment. Today he has no evidence of disease and Glen's Army, a group of family and friends rally to raise funds and awareness for research to find cures.

Diffuse Intrinsic Pontine Gliomas (DIPGs) comprise the most lethal pediatric cancers, being almost completely unresponsive to chemotherapy and intractable for surgical removal. Dr. Reinberg and colleagues found that DIPG cells have an unusual "epigenetic signature" that contributes to their malignancy and have also identified the function of proteins that specifically recognize and translate this epigenetic feature. They are working on a novel therapeutic intervention for DIPGs that entails the identification/generation of reagents that specifically inhibit these proteins from functioning at this DIPG-associated epigenetic signature.

This grant is named for the Making Headway Foundation, a St. Baldrick's partner, whose mission for the past 20 years has been to provide care and comfort for children with brain and spinal cord tumors. The Foundation provides a continuum of services and programs while also funding medical research geared to better treatments and a cure.

Unlike many other pediatric cancers, osteosarcoma has many abnormalities found on genetic analysis of the tumor itself. Dr. Sweet Cordero and colleagues hypothesize that some of these abnormalities could be used to predict what treatment might work best for each specific osteosarcoma patient. For example, many osteosarcomas have genetic alterations that block their ability to "repair" their DNA using specific pathways. One of these defective pathways is called the "homologous repair" pathway and another is called the "alternative lengthening of chromosomes" pathway. The inability of osteosarcoma tumors to repair their DNA using these pathways may make them susceptible to specific drugs. However, it is very likely that these drugs will need to be used in combination and not alone. A key need to advance osteosarcoma patient care is to define and use appropriate model systems to test drugs before using them in patients. This project is combining both preclinical studies in PDX models and a clinical trial to develop new ways to treat osteosarcoma patients with the goal being to improve survival for patients with relapsed and metastatic disease.

This multi-year grant is named for and funded by the Battle Osteosarcoma Hero Fund inspired by and established in honor of Charlotte, Dylan, Tyler and all OsteoWarriors. Led by parents, its mission is to raise funds for promising osteosarcoma precision oncology research to improve treatment options and outcomes for kids battling osteosarcoma.

Malignant rhabdoid tumor (MRT) and atypical teratoid/rhabdoid tumor (AT/RT) are rare but devastating childhood cancers. Most children diagnosed with MRT and AT/RT are under the age of two, and most will die from their disease despite intensive treatment interventions. New insights into what causes these cancers, and new therapies, are desperately needed. Genetically, MRT and AT/RT are simple cancers, caused by loss of just one gene called SMARCB1. If we are to understand and treat MRT and AT/RT, therefore, we need to understand how loss of SMARCB1 causes cancer.

As the recipient of the Oh Danny Boy I Love You So: The Danny O'Brien Rhabdoid Tumor Research Fund St. Baldrick's Research Grant, Dr. Tansey is working on an innovative molecular mechanism through which loss of SMARCB1 causes MRT and AT/RT. He proposes that these mutations drive cancer by stimulating the activity of a known pro-tumorigenic gene called MYC. Dr. Tansey further proposes that MRT and AT/RT can be effectively treated by drugs that block the actions of MYC, currently being developed by us and others. He is testing this model and exploring its therapeutic implications. Completion of this work has the potential to transform the understanding of how MRT and AT/RT form and how they can be treated. Danny O’Brien was five months old when he was diagnosed with a rare malignant rhabdoid tumor on his liver. Despite treatment to shrink the tumor, he passed away at the tender age of 9 months. Fortunately, he knew nothing but love and affection for all of his short life. This fund honors Danny’s courage and remembers his unconditional love in the midst of his battle with cancer.

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.

Adoptive immunotherapy has demonstrated unprecedented clinical success in the treatment of leukemia. In this therapy, T cells are isolated from a patient, expanded outside of the body, and genetically modified prior to reinfusion. The ability of these T cells to recognize and eliminate cancer cells is improved by expressing a protein (CAR) on the T cell surface. This protein increases "specificity," the ability to recognize cancer cells, and "function," the ability to destroy those cancer cells. An important challenge in cellular immunotherapy is to minimize the manipulation of patients' T cells outside the body. Prolonged culture protocols trigger functional exhaustion and compromises their efficacy upon return to the body. A critical issue involves the pre-requisite "activation" step necessary for CAR expression on the cell surface of T cells. By optimizing culture conditions, Dr. Ghassemi developed approaches to express CAR in dormant T cells without the need for activation. Importantly, her preliminary findings show that elimination of this activation step retains effector function and potency of CAR T cells in models of the pediatric cancer ALL. This project is providing insight into the regulatory components influencing CAR expression in dormant T cells which will lead to superior CAR T cells for cellular immunotherapies against ALL.

This grant is supported by TEAM ABBY Gives, a St. Baldrick's Hero Fund. Abby was diagnosed with Pre-B ALL when she was almost five years old. She had a successful bone marrow transplant, but battle battled graft vs. host disease (GVHD) for years. Abby and her treatment team worked hard over many years to keep the GVHD in check. Sadly, Abby passed away on October 19, 2021. This fund unites the incredible support of family and friends in Abby's memory and inspires others to join the fight for cures and better treatments.

Medulloblastoma is the most common malignant brain tumor of children. New approaches to treatment are needed, because current treatment can cause brain injury and fails too many patients. Some medulloblastomas are driven by excessive activity of a signaling pathway called SHH, and for these patients, SHH-pathway inhibitors may offer new hope. Drugs that target an SHH-pathway protein called SMO work against other cancers in other parts of the body. However, medulloblastomas rapidly become resistant when treated with SMO inhibitors.

As the recipient of the Miracles for Michael St. Baldrick's Research Grant, Dr. Sokolsky-Papkov will make SHH-targeted therapy newly effective for medulloblastoma using two innovations. She will use a new combination of two FDA-approved drugs, vismodegib and palbociclib. These inhibitors disrupt two different points in the pathway connecting SHH signaling to tumor growth, preventing resistance that can develop when either drug is administered alone. Furthermore, she has developed a method of packaging these drugs into tiny particles called nanoparticle micelles, which can deliver increased amounts of each drug into brain tumors. Dr. Sokolsky-Papkov hypothesizes that the combination of palbociclib and vismodegib, delivered for the first time in nanoparticle micelles, will advance brain tumor treatment and bring new effectiveness to medulloblastoma therapy.

This grant is named for the Miracles in Memory of Michael Fund created in memory of Michael Orbany who was diagnosed with medulloblastoma when he was six years old. Even through treatment and relapse, Michael had unwavering faith and perseverance, wanting most to make others happy. This fund honors his tremendous strength to never ever give up.

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.

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.

In the U.S., children with a blood cancer called Hodgkin lymphoma (HL) are usually treated successfully. Some of these children will suffer health problems several years later because of the treatment they received. Because of this, doctors use powerful imaging tools to identify patients who are likely to do well or not. Those who are likely to do well require less treatment and those who are less likely to do well can receive more treatment. But in low-income countries like Malawi, these tools are unavailable, and the children there often receive treatment that may be unnecessary. Scientists have found unique abnormalities in adults with HL that can tell us who is less likely to do well. Here, Dr. Ozuah is testing whether these abnormalities are present in children and could be used to decide how best to treat children with HL in low-middle income countries

Ewing Sarcoma (ES) is a type of cancer growing in or around bones in children and young adults. A protein called CD99 is present on all ES cells and inhibition of CD99 by different means kill ES cells. As of today none of these methods of CD99 inhibition is available as a clinical tool. Dr. Uren's team recently discovered that an FDA approved drug, clofarabine, can do the same and kill ES cell by directly binding and blocking CD99. Since clofarabine is already FDA approved, it can be tested on children with ES immediately in a Phase II clinical trial. Clofarabine is currently used in leukemia patients in the clinic due to its ability to inhibit different proteins in the cell. Since his findings suggest that there is a novel mechanism that was not known before, it is critical to establish how exactly inhibition of CD99 in ES cells lead to their death. That knowledge is the key to initiate a Phase II clinical trial with ES patients. This project will provide the missing information and accelerate design of new clinical trials based on CD99 inhibition.

Although patients with certain types of brain tumors are frequently cured by well-established treatments, patients that experience tumor relapse have limited treatment options and frequently succumb to their disease. In addition, the side effects resulting from radiation therapy result in lifelong and devastating cognitive impairment. As the recipient of the Making Headway Foundation St. Baldrick's Research Grant, Dr. Sarosiek recently found that decreasing the expression of BET proteins with a targeted drug can enhance the radiation sensitivity of brain tumors while reducing radiation sensitivity in healthy brain cells, thus supporting increased cure rates and decreased treatment-associated toxicities. In this project, Dr. Sarosiek is directly testing the sensitivity of medulloblastomas to BET inhibitors, alone and in combination with radiation therapy and chemotherapy; and determining the extent to which BET inhibitors can protect critical brain cells from radiation treatment. Importantly, BET inhibitors are currently being evaluated in clinical trials for other cancers and are thus readily available for clinical deployment for treatment of pediatric patients with medulloblastomas. Knowledge gained in these studies will serve as a foundation for the testing of BET inhibitors in clinical trials in children diagnosed with medulloblastomas and potentially other CNS tumors to dramatically improve treatment outcomes.

This grant is named for the Making Headway Foundation whose mission for the past 20 years has been to provide care and comfort for children with brain and spinal cord tumors through a continuum of services and programs while also funding medical research for cures. 

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.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor that has a very poor prognosis despite aggressive treatment. The development of new, effective therapeutic approaches for AT/RT has been hindered by a lack of specific therapeutic targets. It is necessary to find effective therapeutic targets, preferably based on the understanding of the molecular mechanisms that promote this highly malignant brain tumor. A tumor suppressor gene (SMARCB1) is absent in the majority of AT/RT and loss of this gene leads to factors that promote tumor growth. This research involving genetic and pharmacologic inhibition of histone binding proteins (EZH2 and BRD4) is of high importance for developing effective therapies for pediatric patients with AT/RT. Dr. Hashizume will determine whether therapeutic combination of targeting two histone binding proteins, BRD4 and EZH2, provides synergistic benefits, and will inform how best to maximize the clinical potential of combination therapy for effective treatment of children with AT/RT. This research will also test how tumors adapt to this molecular targeted therapy, to ultimately inform clinicians how to treat tumors that have resistance to molecular targeted therapy. Finally, this project will explore how this combination therapy interacts with radiation in treating AT/RT, which is important due to the frequent use of radiation in treating AT/RT.

This grant is generously supported by the “Just Do It…and be done with it” St. Baldrick’s Hero Fund created in honor of Sara Martorano who was four years old when she was diagnosed with Stage IV Wilms tumor. Thanks to research, today she is cancer free. This fund celebrates the courage of cancer kids through treatment and the support of their family and friends.

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.

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.

This year it is estimated that 800 children will be diagnosed with osteosarcoma. It is thought that sex hormones play a role in the onset of the disease, as more boys than girls get osteosarcoma and the cancer develops at the time of puberty. Dr. Miranda hypothesizes that a key molecule in estrogen signaling is turned off in osteosarcomas, preventing those cells from being normal bone. Her preliminary data shows that she can turn back on that key estrogen signaling protein. These drugs have not been tested in osteosarcoma patients, but are FDA-approved drugs, so they could provide a treatment for osteosarcoma patients in the immediate future.

This grant is generously supported by the Sweet Caroline Fund created to honor the memory of Caroline Richards who was diagnosed with osteosarcoma at age 11. She persevered through rigorous treatments with a giving spirit and a contagious smile, always thinking of how to make others happy or laugh. This fund pays tribute to her compassion for others by supporting osteosarcoma research to help kids with cancer

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.