Grants Search Results

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.

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.

Based on progress to date, Dr. Summers was awarded a new grant in 2020 to fund an additional year of this Fellow award. Early T-precursor ALL (ETP-ALL) is a type of leukemia that is often difficult to treat with currently available chemotherapy. As a result, children with ETP-ALL have high rates of relapse of their leukemia and poorer survival rates than children with other types of ALL, and require more treatment with chemotherapy, often leading to long-term toxic side effects. For these reasons, new treatments for ETP-ALL are needed. MERTK is a protein that is found on the surface of some leukemia cells, including ETP-ALLs. Recently, Dr. Summers and colleagues developed a new medicine that has few toxic side-effects and can be used to kill leukemia cells that have MERTK on their surface. Funded as the Emily Beazley's Kures for Kids Fund St. Baldrick's Fellow, this grant will allow him to test whether and how this new medicine could be used to more effectively treat children with ETP-ALL, leading to improved outcomes and better quality of life.

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.

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.

NUT midline carcinoma (NMC) is a deadly cancer that affects children and young adults, with a survival of less than 7 months. NMC is caused by a protein called BRD4-NUT that changes the structure of DNA in such a way that the DNA drives expression of cancer-associated genes that promote growth of NMC. Dr. French proposes to determine what is actually happening to the structure of the DNA that allows it to express the cancer-driving genes. There are two protein types he suspects are helping BRD4-NUT distort the DNA conformation; these are called HDACs and HATs. Dr. French's team will use state-of-the-art inhibitors that target specific HDACs and HATs to determine their respective roles and help identify novel therapeutics to treat this incurable disease.

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

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 sarcomas are bone cancers that impact many adolescents and young adults. Despite the use of intensive traditional chemotherapy combined with advanced surgical techniques, 30-40% of patients still die after the disease eventually spreads to other organs, such as the lungs and bone marrow. Dr. Hayashi's team believes the key to overcoming this problem lies in the identification of “Circulating Tumor Cells (CTC)”. These are cells that break away from the original tumor and travel through the blood stream, eventually taking root in another organ to form what is called metastatic disease, meaning the cancer has spread from where it started into different areas of the body. These cells undergo multiple changes in order to leave the original tumor and survive in the harsh environment of the blood stream, eventually leaving the blood stream to invade another organ where they multiply and grow. This project aims to dissect each of these complicated steps with the goal of unveiling which element of this devastating process can be targeted to disrupt it.

Despite recent advances in technology, very little is known about many types of rare and high risk childhood cancers. Since the numbers of these patients are so small, it has been very difficult to study how best to take care of them. Dr. Potter is using technology to look at the genetic code of these rare tumors, in order to learn more about why and how they occur, as well as how they change over time. This knowledge will help to create tests to diagnose these patients, as well as to develop more effective, less toxic treatments.

This grant is generously co-supported by the Invictus Fund and O Danny Boy I Love You So: The Danny O'Brien Rhabdoid Tumor Research Fund. The Invictus Fund was created to honor the memory of Holden Gilkinson who was diagnosed with Stage IV anaplastic Wilms tumor when he was 3 years old. Holden endured intense treatment and surgery, eventually losing both kidneys. He passed away just a few days shy of his 7th birthday. Through it all, Holden’s unconquerable spirit and love for life prevailed and is personified in the poem “Invictus” by William Ernest Henley. Danny O’Brien was just 5 months old when he was diagnosed with a malignant rhabdoid tumor on his liver. This cancer is extremely rare and aggressive. He endured chemotherapy to shrink the tumor for surgery, but the treatment was not effective. At the tender age of 9 months, Danny passed away. Fortunately, he knew nothing but love and affection all of his short life. This fund honors Danny’s courage and his unconditional love even in the midst of his battle with cancer.

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.

As the recipient of the Rosa and Francesco Romanello St. Baldrick's Research Grant, Dr. Lawlor is studying an aggressive tumor called Ewing sarcoma that occurs most often in teenagers. It usually starts in a bone and then can spread or metastasize throughout the body. Once it has spread, the chances of cure are very poor. She is studying how the tumor cells change the surrounding normal tissues to allow the tumor cells to leave the bone and spread to other sites in the body. Results so far have shown that the tumor cells and the normal tissues "talk to each other" and that this crosstalk is likely to be essential for the growth and spread of the tumor, both within the bone as well as in other tissues. Dr. Lawlor will decipher these messages, and the instructions they convey, so that new therapies can be developed that will intercept them and block tumor spread.

This grant is named in recognition of Salvatore Romanello for his decade of service as pro bono general counsel to the St. Baldrick's Foundation. He has chosen to name the grant in honor of his parents who instilled in him the values of generosity and caring for a greater cause.

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.

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.

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.

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.

Although many children being treated for cancer initially respond to therapy, cancer cells often become resistant to chemotherapy drugs. Drug resistance is a major cause of cancer relapse, recurrence, and treatment failure. Dr. Gordon's goal is to identify new approaches to block, or reverse, resistance to an important class of cancer drugs. He has already identified one approach to reverse resistance in the laboratory, which he is now testing in models of cancer. Dr. Gordon is also testing a large number of additional drugs for the ability to prevent or reverse resistance.

Radiation therapy is an important tool in the treatment of childhood cancer. Radiotherapy not only makes tumors shrink, it also causes inflammation of the tumor and can make immune cells attack the cancer. However, tumor cells can secrete substances that prevent immune cells from killing cancer cells. In addition, certain immune cells, called regulatory T cells (Treg) and myeloid derived suppressor cells (MDSC), exist to prevent an overshooting immune response. These cells are recruited to inflamed tumor tissue and dampen the anti-cancer immune response. To overcome this problem, Dr. Otto is testing a drug in combination with radiotherapy that has shown to reduce or deplete immunosuppressive cells from tumors, and lead to increased numbers of cancer killing immune cells in the cancer tissue. In models of pediatric cancer, he is combining this drug with a particular form of radiotherapy, called radionuclide therapy that uses radioactive substances which are injected into the bloodstream to carry their radioactive load directly to tumor cells. Dr. Otto hopes that this combination therapy will lead to robust and long-lasting anti-cancer effects.

This grant is made with generous support from the Team Campbell Foundation, established in memory of Campbell Hoyt, who courageously battled anaplastic ependymoma, a rare cancer of the brain and spine for five years. Its mission is to improve the lives of families facing a childhood cancer diagnosis through raising awareness, funding research and providing psycho-social enrichment opportunities.

There is a new and effective cancer treatment for some incurable pediatric blood cancers. The treatment involves programing a patient's own cells to destroy their tumor, a process called cellular immunotherapy. Despite great effort to use cellular immunotherapy to treat 'solid' tumors, which include tumors of the bones, muscles and other parts of the body, we have not been successful yet. One major reason is that the programmed patient cells are designed to recognize a single marker on a cancer cell. In some blood cancers, all of the tumor cells express the same marker increasing the likelihood that cellular immunotherapy can cure the patient. Solid tumors are more heterogeneous than blood cancers, meaning each solid tumor cell may express a different marker. Therefore, cellular immunotherapy is less likely to destroy all solid tumor cells and the chances of achieving a cure is much more difficult. A potential solution is to trigger the body's own immune system to destroy tumor cells that express many different markers, a process called "epitope spreading". Named as the David's Warriors St. Baldrick's Scholar, Dr. Leibowitz focuses his project on testing strategies to augment epitope spreading in pediatric solid tumors so that cellular immunotherapy may become an effective and viable treatment option in the future.

This grant is named for and generously supported by the David’s Warriors Hero Fund created in memory of David Heard who battled neuroblastoma and inspired his family and countless others to commit to raising money for research to fight pediatric cancer. This fund honors the amazing spirit in which he lived, embracing life until the very end.

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.