Grants Search Results

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.

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.

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

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.

Pediatric brain tumor patients are at risk for deficits in cognitive functioning, including attention, memory, and processing speed. Evaluation of these functions by neuropsychologists is important for connecting patients with appropriate interventions to reduce academic or vocational difficulties. Despite the importance of neuropsychological services, traditional assessments are time consuming and costly for both providers and families. As such, neuropsychological surveillance is often limited. Due to advances in technology, computerized neuropsychological batteries were developed that can be completed via internet in the home. As the recipient of the Grace for Good Fund St. Baldrick's Supportive Care Research Grant, Dr. Raghubar is determining if children diagnosed and treated for brain tumor can successfully complete web-based tests. Patients currently receiving annual neuropsychological evaluations will be asked to complete a web-based battery. She will evaluate 1) the rate of successful completion; 2) the relationship between performance on the computerized and traditional neuropsychological tests; and 3) the degree to which patients are similarly categorized as demonstrating impaired versus non-impaired neurocognitive abilities when assessed using either form of assessment. This line of research has the potential to improve the clinical care of patients and survivors. She may also find a solution to the problems that have plagued late-effects research for decades, such as poor participation and high dropout rates.

This grant is named for the Grace for Good Fund in honor of Grace Carey and celebrates her survivorship from medulloblastoma. While Grace handled her treatments with minor setbacks, she now faces challenges wrought by the very medications and procedures that saved her life. This fund was inspired by her desire to help other kids with cancer and supports research of brain tumors and the multitude of challenges facing survivors post treatment.

Despite cure after cancer, the majority of childhood cancer survivors are diagnosed with chronic health problems such as diabetes, hypertension, or heart disease within 30 years of cancer diagnosis and treatment. Hypertension and diabetes are important health problems associated with heart disease and result in early death compared to survivors without heart disease. Compared to siblings, childhood cancer survivors treated with radiation have a higher risk of developing diabetes at a young age. Even though important, the reasons for developing diabetes in cancer survivors are poorly understood. Insulin is an important hormone and affected by cancer treatment. Dr. Mostoufi-Moab is for the first time examining cancer treatment effects (radiation vs. chemotherapy) on making insulin and breaking down blood sugar in childhood cancer survivors, age 15-30 years. She will use tests to measure glucose breakdown, insulin secretion, and mathematical modeling to evaluate the body's handling of fat, all important steps for understanding the why cancer therapy causes diabetes in CCS. Understanding the steps leading to diabetes will help doctors chose the correct treatments for diabetes and for scientists to test options to prevent diabetes in cancer survivors. Achieving these goals will improve quality of life and avoid early death due to cancer treatment-related conditions in childhood cancer survivors.

Many chemotherapy drugs used in childhood cancer have the potential to damage peripheral nerves and thus may impact a child’s ability to function. Early detection of this nerve damage is important to tailor treatment plans and initiate rehabilitation interventions. Currently, no measure of chemotherapy-induced peripheral neuropathy (CIPN) exists that is appropriate for use in children ages 1-4 years, an age group that is more commonly impacted by a number of childhood cancers. Thus, Dr. Gilchrist is finalizing the development of a scale of CIPN specifically tailored for young children that focuses on eliciting responses to test nerve function (such as tendon reflexes and strength of muscle groups) as well as developmentally appropriate measures of motor function (such as grasping an object or standing on one foot). She is also comparing results from 25 children ages 1-4 years being treated for cancer with neurotoxic treatments and 25 age and gender-matched controls to determine if the measure is both reliable and valid. If successful, she will be able to provide an objective measure for this common treatment side-effect that should positively impact both research and clinical care for these young children.

With increased survival for children with cancer, efforts that prevent long-term health problems are important for improving the quality of life and life expectancy of these children. Diet and fitness are two critical factors for healthy survivorship, but interventions for survivors of childhood cancer have had limited impact, focus almost exclusively on physical activity, and often exclude caregivers, the primary nutrition gatekeepers in the home. Although research supports a key role for the gastrointestinal (GI) microbiome in regulating weight and health outcomes, no studies have examined the “obesogenic” microbiome in the context of interventions for these survivors. Harvesting Hope for Kids (HH4K) is a unique, biobehavioral lifestyle intervention delivered over 8 weeks during the summer in a university-based, cancer survivor garden. It was adapted from a successful intervention for survivors of adult-onset cancer, with pilot data supporting its feasibility in children. In line with St. Baldrick’s mission to improve outcomes for children with cancer, this randomized controlled trial is evaluating the efficacy of HH4K to improve dietary and physical activity patterns in 40 survivors of pediatric cancer (i.e., ages 8-12; < 2 years off treatment). Results will support a larger, multi-institutional trial and improve survivorship care to prevent costly, long-term morbidity.

This award allows Dr. Parsons the freedom to pursue discovery without the restrictions of a normal grant. The questions he is exploring include: What are the biologically and clinically-relevant genomic alterations in high-risk and rare pediatric cancers? What are the most useful and cost-effective clinical sequencing tests for childhood cancer patients? How can clinical genomics/precision oncology be most effectively implemented for diverse patients and families in varied clinical settings? What clinical benefit can precision oncology approaches and the use of molecularly-targeted therapies offer to childhood cancer patients? He is optimistic that a "team science" approach, bringing together investigators from diverse disciplines, departments, and institutions, will continue to yield critical data and discoveries that guide pediatric cancer research and clinical care in the next decade.

Some childhood cancers do not respond to chemotherapy, surgery, or radiation. For these patients, researchers are developing a new set of treatments that use their own immune system to attack the cancer. To turn on these defenses, they need to bolster the DNA in 200 million immune cells, efficiently and safely. Unlike other strategies, these cells do not need to come from the patients, who are already weakened. Dr. Weiss has invented an engineering solution to do so and is testing it so that he can make this treatment widely available to patients and their doctors soon.

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.

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.

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. 

Millions of cells are formed every day in the developing brain of children. Medulloblastoma, a pediatric tumor, occurs when the proliferation of cells in the cerebellum (a lower part of the brain) becomes uncontrolled. The Notch pathway is a key mechanism that governs cell proliferation in many biological contexts. Aberrant up-regulation of Notch signals is associated with medulloblastoma. Re-gaining control of Notch could help cure medulloblastoma patients. As the recipient of the Hope for Daisy Research Fund for Pediatric Brain Tumors St. Baldrick's Research Grant, Dr. Rual's goal is to better understand the molecular mechanisms that control Notch signals in brain cells and, thus, to define novel therapeutic targets for the benefit of medulloblastoma patients. He recently identified the L3MBTL3 gene as a new modulator of Notch signals. Importantly, previous studies have shown that the L3MBTL3 genes is deleted in medulloblastoma patients. Dr. Rual hypothesizes that the L3MBTL3 deletions observed in medulloblastoma patients result in the aberrant regulation of Notch signals, thus supporting tumorigenesis. Dr. Rual's team will test this hypothesis by studying the extent to which inhibiting L3MBTL3 modulate medulloblastoma tumor progression in models of medulloblastoma. This study could offer critical mechanistic insights on the role of the L3MBTL3 in medulloblastoma that could be harnessed in the future for the therapeutic benefit of medulloblastoma patients.

This grant is funded by and named for the Hope for Daisy Research Fund for Pediatric Brain Tumors, a St. Baldrick's Hero Fund. Diagnosed with medulloblastoma at the age of six, Daisy Walsh met the challenge head on with joy, strength and laughter. Days before her eighth birthday, the tumor recurred and despite her brave battle, Daisy passed away in February 2020. This fund honors her courageous spirit by helping to raise awareness and funds for research to increase survival rates and hope for all children battling brain cancer.

The goal of Dr. Riehle's research is to find a cure for a rare form of liver cancer that occurs in children and young adults, called fibrolamellar hepatocellular carcinoma (FL-HCC). Unfortunately, surgery is currently the only effective treatment option for these patients, and once the disease has spread outside of the liver there is no chance for cure. Dr. Riehle's laboratory has spent the last few years trying to understand what changes within the liver cause healthy kids to get this cancer, and has developed a couple of new models of FL-HCC that can be used for drug screening. In this project she is using these models to test new treatment options and to try to understand how this cancer develops.

Cure rates for pediatric acute myeloid leukemia (AML) have remained at or below 60% for decades, and the largest reason for treatment failure is relapsed disease. Once relapse happens, it is very difficult to cure the disease. It is well known that interactions between AML cells and the non-cancerous supportive cells in the bone marrow, called stromal cells, can protect leukemia cells from chemotherapy. Dr. Redell's team reported that an enzyme in AML cells, called spleen tyrosine kinase (SYK), is turned on when AML cells contact stromal cells, and SYK helps AML cells survive chemotherapy. She will further investigate this enzyme, using a large panel of AML cells that come directly from pediatric patients. The drug company Gilead Sciences has given Dr. Redell a supply of their new SYK inhibitor, entospletinib, to test in her studies. To make sure that the results of the drug testing are related to blocking SYK, she also has made some AML cells that do not make SYK. Dr. Redell's team will do experiments to learn how SYK helps AML cells resist chemotherapy, and they will test entospletinib in AML models to determine if it might be a good drug to add to chemotherapy for patients.

Juvenile myelomonocytic leukemia (JMML), a fatal childhood blood malignancy, has limited therapeutic options. Relapse remains the main cause of treatment failure, most likely due to the persistence of leukemic stem cells (LSCs), a small population of self-renewing precursor cells that give rise to the bulk of tumor cells. Dr. Qu is exploring an innovative approach to eradicating LSCs in a subset of JMML that is caused by genetic mutations in Ptpn11. The information gathered from this study may yield a novel strategy for the treatment of this particular type of JMML.

Medulloblastoma is one of the most common malignant brain tumors in children. The Group 3 subgroup tumors have the poorest outcomes due to dissemination of tumor cells to distant sites in the central nervous system. As the recipient of the Benicio Martinez Fund for Pediatric Cancer Research St. Baldrick's Research Grant, Dr. Pei has identified a subpopulation of tumor cells that contribute to the metastasis after radiotherapy. He is determining whether targeting these cells can eliminate or prevent metastasis of Group 3 medulloblastoma, thereby improving the outcome of patients with this disease. Weeks after being the top fundraiser in his 6th grade class and shaving his head at his school’s event, Benny was diagnosed with medulloblastoma. Despite complications from treatment and setbacks, Benny has an amazing can-do attitude and is battling the cancer with determination.

This grant is funded by the Hero Fund that honors Benny’s fight and supports cures and better treatments for kids like him.