Grants Search Results

Myelodysplastic Syndrome (MDS) are clonal stem cell disorders characterized by abnormal cell growth and shape, lack of mature blood cells, and increased risk of acute myleoid leukemia (AML) development. Approximately 10,000 new cases are diagnosed every year in the United States. Survival ranges from months to years, and bone marrow transplantation remains the only cure. To identify new drug targets associated with more specificity and less morbidity and mortality, it is essential to understand the molecular course of MDS. Unbiased sequencing studies have identified over 45 recurrent somatic mutations in MDS patient samples. Of these pathways, splicing factor and epigenetic regulator mutations are the most common. Point mutations in splicing factor 3b subunit 1 (SF3B1) are found in less than 25% of MDS patients. Dr. Wallace and colleagues have shown that mutations in SF3B1 lead to an altered function, name upstream cryptic 3 splice site selection. Epigenetic regulators, including the de novo DNA methyltransferase, DNMT3A, are the second most common class of mutations identified in MDS. Studies on the effect of loss of DNMT3A expression have primarily been limited to the effects of altered methylation in regions outside of the gene body, such as enhancer accessibility. Although sequencing studies have shown that both splicing factor and epigenetic regulator mutations commonly co-occur as early mutations in MDS pathogenesis, it is unknown how altered DNA methylation and aberrant mRNA splicing can cooperate to promote MDS progression. Using cell line and animal model systems, Dr. Wallace will determine whether the cooperation of epigenetic regulator and splicing factor mutations lead to a more aggressive form of MDS. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

Diffuse intrinsic pontine glioma (DIPG) is a deadly pediatric brain cancer. Tragically, the majority of children diagnosed with the disease die within 12 months because the most effective treatment, radiation, is palliative at best. Therefore, there is a significant need to develop new therapeutic strategies to improve the terrible outcomes for these patients. Looking at genes that are turned on or off in a cancer can be helpful to figure out what is causing cancer growth. DIPGs are known to have mutations in a group of genes called histones that intriguingly regulate whether other genes in the cell are turned on or off. While looking at genes that are turned on or turned off in DIPG, Dr. Tsai found a gene called FOXR2 that is turned on in a subset of these tumors. FOXR is not usually present in the normal brain, but it has high levels in a subset of DIPGs. This is exciting because if researchers can target FOXR2 with new therapies, only tumor cells would be affected, sparing the normal cells in the brain. The goal of this project is to figure out exactly how FOXR2 makes DIPGs grow and to identify strategies that can be used in new treatments to target FOXR2.

A portion of this grant is generously supported by Griffin's Guardians, a St. Baldrick's partner. Griffin's Guardians was created by the Engles in memory of their son, Griffin. Their mission is to provide support and financial assistance to children battling cancer in Central New York, raise awareness about pediatric cancer and provide funding for research.

Neuroblastoma is one of the most common pediatric tumors, responsible for 12% of all cancer deaths in children under 15 years old. Only about 50% of patients with widespread neuroblastoma will live for ten years after diagnosis. A recent breakthrough in cancer treatments known as CAR T cell therapy reprograms a patient’s own immune cells to recognize tumor cells. While CAR T cell monotherapy works for some cancer types, several research studies using CAR T cells to treat neuroblastoma have been relatively unsuccessful. This is likely due to immune suppression caused by the tumor itself. Interestingly, it is known that if a person with cancer develops an infection, the infection can stimulate an immune response that will promote cancer remission. With this knowledge, Dr. Kudek and colleagues have pioneered an innovative technique to boost CAR T cell therapy response. They have shown that the cancer-destroying function of reprogrammed immune cells is boosted when a weakened infection is introduced into a tumor and found that this treatment combination in bladder cancer led to cure in most of the disease models. Encouraged by these findings, he is pursuing proof-of-principle studies to determine how this treatment approach can be best applied to neuroblastoma treatment.

This grant is named for the LukeStrong a Force Against Neuroblastoma Childhood Cancer Fund. When Luke was 5 years old, he was diagnosed with high-risk neuroblastoma. He is now in his teens and still in active treatment for relapsed neuroblastoma. Since 2014 Luke’s “Never tell me the odds” attitude has inspired his family and friends to shave their heads, fundraise with St. Baldrick’s, and help conquer childhood cancers.

Children with some kinds of blood cancers (leukemias) are not cured by regular chemotherapy and are at high risk of dying without better treatment options. Dr. Niswander is working to create new treatments that are more personalized for each child’s leukemia cells. The first treatment targets ‘miswired’ communication networks inside the leukemia cells that make them cancerous, and the second treatment uses the body’s own immune system to attack the leukemia cells. Each of these treatments is able to kill a patient’s cancer cells. But, eventually the leukemia cells develop changes that allow them to begin growing again despite the therapy, and the cancer comes back. These two therapies have never been combined together in patients. In this project, Dr. Niswander and colleagues are studying the best ways to combine these new treatments for two kinds of high-risk pediatric leukemias, since often two treatments that work in different ways are better than one. She is hopeful that by using patients’ own leukemia cells they will identify the best personalized treatments for future testing in pediatric patients to improve their chances of cure and living long and healthy lives.

For 2022, this grant is named for the Invictus Fund, a St. Baldrick’s Hero Fund created in memory of Holden Gilkinson. It honors Holden's unconquerable spirit in his battle with bilateral Wilms tumor by funding cures and treatments to mitigate side and late effects of childhood cancer.

In 2021, this grant was generously supported by Super Soph's Pediatric Cancer Research Fund, a St. Baldrick's Hero Fund. Sophie Rossi was diagnosed with AML at 3 months of age. Throughout her courageous battle, she was always smiling, always joyful. This fund was created to honor her spunky, sweet spirit by funding research to find cures for AML and all childhood cancers.

Bone marrow transplantation is a highly effective treatment for relapsed and difficult to treat forms of pediatric leukemia, but unfortunately has a high risk for dangerous side effects. Viral infections are a major problem in the weeks and months after bone marrow transplant while children's immune systems are still immature. These infections can be debilitating and even deadly while also being very difficult to treat since available antiviral medications frequently do not work. Over the last few years, researchers have had great success in combating these viral infections by taking T-cells (a type of infection fighting cell that is part of the immune system) donated by children's personalized stem cell donors and engineering them to attack and kill certain viruses. Additionally, the rates of side effects using this therapy have been incredibly low. Dr. Rubinstein now intends to offer this therapy as a preventative measure, with the hope that this strategy will decrease the number of patients suffering from dangerous viral infections after bone marrow transplant. This clinical trial has the potential to decrease the number of pediatric cancer survivors who die from infection while also shortening hospitalizations and decreasing the need for other anti-viral medications.

This grant is generously supported by the Rally for Ryan Fund, a St. Baldrick's Hero Fund. Ryan was diagnosed with ALL when he was 7 years old and began treatment immediately. Initially labeled “high risk” due to a poor response, he completed 3½ years of a difficult treatment protocol before relapsing 11 months later. After his third relapse and an unsuccessful immunotherapy trial, Ryan had a bone marrow transplant in December 2020. He is currently fighting graft vs. host disease but is doing well and is optimistic for a good response. The Campanaros created this Hero Fund to celebrate Ryan’s courageous spirit and knowing firsthand the importance of research, to raise funds to find better treatments for kids with cancer.

Based on progress to date, Dr. Reitman was awarded a new grant in 2022 to fund an additional year of this Fellow award. Brainstem gliomas are deadly brain tumors that affect children. The only effective treatment is radiation therapy, but despite this treatment all children with this disease eventually experience growth of the tumor and eventually death. As the Emily Beazley's Kures for Kids Fund St. Baldrick's Fellow, Dr. Reitman will test if treatments that enhance the efficacy of radiation therapy can improve survival in the laboratory. This could lead to new clinical trials aimed at helping children with brainstem gliomas to survive longer.

This grant is funded by and named for Emily Beazley's Kures for Kids Fund. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma and battled through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle, inspiring a community to come together to show love and change lives. She had a dream of starting a foundation to fund research and named it “Kures for Kids”. Today, Emily's family and friends carry on her dream and her mission in her memory.

Over-expression of HOXA9 protein in acute leukemias, which are cancers of the blood, is associated with worse outcomes. This over-expression occurs in more than 50% of acute myeloid leukemia (AML) cases and in approximately 75% of infant acute lymphoblastic leukemia (ALL) cases. In the laboratory setting, decreasing the level of HOXA9 in AML cells has been shown to reduce their growth. This project aims to develop a way to target HOXA9 in AML and infant ALL using short segments of DNA called oligonucleotides designed to decrease HOXA9 protein or prevent its function. The use of oligonucleotides as drugs has recently been successful in the treatment of various disorders. The goal of these studies is to eventually lead to the use of oligonucleotides as novel therapeutic agents in a clinical trial setting for treatment of AML and infant ALL.

Leukemia is the most common form of childhood cancer. While most children with leukemia can be cured, patients whose leukemia comes back after an initial response to therapy are very difficult to treat and often die of their disease. As the Ty Louis Campbell Foundation St. Baldrick's Fellow, Dr. Levinson studies one of the classes of medicines used to treat leukemia called "glucocorticoids" (a type of steroid), in a type of leukemia called T-cell ALL. Though glucocorticoids are usually very good at killing leukemia cells, some patients have been found to not respond (or be "resistant") to glucocorticoids, while others develop resistance over time, making their disease far more difficult to treat. Dr. Levinson's research is focused on understanding how and why such resistance develops in an effort to identify ways to overcome it and, ultimately, increase the percentage of children with T-cell ALL who can survive their disease.

This grant is funded by and named for the Ty Louis Campbell Foundation, a St. Baldrick's partner, created in memory of Ty Louis Campbell who lost his battle with brain cancer at the age of five. The Foundation seeks less toxic, more effective treatments that are specifically designed for children fighting cancer. Their ultimate mission is to help fund the intelligence and technology that will uncover new ways to cure children with cancer.

Most children diagnosed with cancer today will survive but will develop late complications of their cancer treatment. Childhood cancer survivors have almost twice the risk of diabetes compared to other adults. Diabetes is known to increase the risk of heart disease among survivors, and heart disease is the leading cause of non-cancer death among survivors. Prediabetes is easily diagnosed and begins months to years before diabetes. However, little is known about prediabetes risk-factors and prevention in survivors, despite reports that up to 1 in 3 survivors have prediabetes. Using treatment information and recent assessment of over 3,500 adult survivors of childhood cancer, this research will identify the extent of prediabetes among survivors, characterize what cancer-treatments increase risk, and determine how quickly these survivors develop diabetes. Research will then establish if a medication and lifestyle intervention to prevent diabetes in prediabetic survivors is safe and achievable. This will inform a future diabetes intervention trial with the goal of improving long-term survival and quality of life for childhood cancer survivors.

Based on progress to date, Dr. Conneely was awarded a new grant in 2022 to fund an additional year of this Fellow award. Acute myeloid leukemia (AML) is the second most common blood cancer in children and is difficult to cure. About one quarter of children with AML have a form of the disease called core binding factor (CBF) AML. Despite intense therapy, cancer will come back in one out of three children with CBF-AML. We want to find new ways to treat this common form of AML by learning how the specific combination of mutations in the cancer cells affect their ability to grow and survive. Some patients with CBF-AML have unique mutations that can stop cells from correctly fixing damage, allowing them to grow too quickly. The project will study how these mutations contribute to CBF-AML cells' development, growth, and survival, affecting the cancer cells' ability to grow using cancer cells with these unique mutations. This will help in understanding how this type of AML develops, and may lead to new ways to treat children with this disease.

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

There are new cancer therapies in which a patient's own immune system is retrained to fight against their cancer. In one of these therapies, known as CAR-T cells, a patient's immune cells are removed from the bloodstream and reprogrammed to target and attack their cancer when the cells are returned to the body. While this therapy has shown great promise, there are still situations, especially with very high-risk cancers, where it does not work. One significant issue that exists with this treatment is that the retrained immune cells do not always stick around after being given back to the patient, which allows the cancer to outlast the therapy and come back. We know that once cancers have resisted a treatment once, it is difficult to use the same treatment again. This projects aims to find ways to alter tumor-targeting immune cells to make them last longer when they are given back to patients, ultimately allowing for a long-term cure for their cancer without the need for further treatment.

This grant is generously supported by the TeamConnor Childhood Cancer Foundation. TeamConnor Childhood Cancer Foundation's mission is to raise funds for national childhood cancer research programs, to build awareness that only a fraction of the NIH’s annual funding supports childhood cancer research, and to support inpatient programs. Founded in 2008 in honor and memory of Connor Cruse, TeamConnor has funded over $4M in pediatric cancer research grants across the United States.

Lymphoma and leukemia are cancers that often strike children. Some types of these cancers cannot grow or survive without a protein called MALT1. As the Do It For Dominic Fund St. Baldrick's Fellow, Dr. Maurer found that, in some lymphoma cells, when the level of another protein called GRK2 was lowered, it led to more action of the MALT1, and more cancer growth. So, she thinks that GRK2 might be working to stop lymphoma tumors by blocking MALT1. She is working to find out two things: Does the level of GRK2 also affect the growth of leukemia? And how exactly does GRK2 interact with MALT1 to block its tumor-growing action? Understanding this interaction will help to design new treatments that work by blocking the MALT1 and stopping the growth of lymphoma cells, and perhaps leukemia cells too, so that children can be cured.

This grant is named for the Do It for Dominic Fund which honors the memory of Dominic Cairo who battled non-Hodgkins lymphoma and was a hero to his school and community. His family and friends continue to raise funds and support research in the hopes that no child has to go through what Dominic endured.

Eight out of ten children with cancer will be cured and will become long-term survivors. However, children with cancer experience serious side-effects during, and even after, finishing treatment that negatively affect their well-being. There is also variation and unpredictability in who will experience these side-effects. Additionally, despite the best treatments, some children are not cured and ultimately lose their fight against cancer. Dr. Wadhwa is examining the role played by body composition (fat and muscle) of children with cancer on side-effects and cure rates. The dose of chemotherapy has been based on height and weight. Dr. Wadhwa and colleagues believe that body composition plays an important role in how the chemotherapy is distributed in the various compartments of the body. They are using routinely performed CT scans to determine body composition and plan to identify a method to personalize the chemotherapy dose for each child and minimize serious side-effects but at the same time, maximize cure rates.

Children and adolescents everywhere in the world get cancer and both the type of cancer, and perhaps more importantly, where they live in the world, factor into whether they live or die. This is due to major disparities between countries in access to optimal treatment, early abandonment of therapy despite the potential for cure, and availability of quality supportive care. Acute lymphoblastic leukemia (ALL), the most common childhood cancer, is mostly curable in countries with strong health systems, like the United States. However, we do not know the exact number of children and adolescents who develop and die from ALL worldwide, because many countries with limited resources also lack quality health registration systems. Identification of context-appropriate strategies to prevent future deaths in children with ALL are necessary, and when combined with improved burden estimates, can guide policy decisions more effectively. Knowing that the majority of countries in the world have limited resources, this project will determine what the best interventions are to improve outcomes for children and adolescents with ALL now, while testing ways to improve estimates of the number of children with ALL who are currently not correctly diagnosed or do not reach healthcare. Awarded at St. Jude Children's Research Hospital and transferred to University of Washington.

Neuroblastoma is a common solid tumor in children, accounting for 1 in 10 new cancer diagnoses. Approximately half of the children with the high-risk form of the disease will die, and the survivors will bear a lifelong burden from the intensity of therapy. We are desperately in need of novel treatment approaches. The most aggressive neuroblastomas have extra copies of a gene called MYCN, which causes neuroblastoma cells to have different metabolism from normal cells. As the Mighty Micah's Mission Fund St. Baldrick's Fellow, Dr. Maxwell is investigating the abnormal metabolism of neuroblastoma in order to uncover new potential therapies. He has found that the amino acid, asparagine, is critical to the growth and survival of neuroblastoma, and has identified two medications (called DON and asparaginase) that, when combined, reduce the levels of this critical nutrient and effectively kill the most aggressive neuroblastomas. This work could serve as the basis for new clinical trials with this drug combination in children with neuroblastoma. Dr. Maxwell aims to exploit neuroblastoma's metabolic Achilles' heel in order to improve outcomes for children who suffer from this devastating disease. This approach holds great promise for future targeted therapies to treat not only neuroblastoma, but many other cancers that rely on abnormal metabolism.

This grant is named for Mighty Micah's Mission Fund, a St. Baldrick's Hero Fund. Diagnosed when he was 15 months old with high risk neuroblastoma, Micah was in treatment for nearly 7 years and survived two relapses. Thanks to research supported by St. Baldrick’s and the development of a new drug that is less toxic and more effective, Micah has no evidence of disease today. He has been named a 2020 Ambassador for St. Baldrick’s and as a science fan who hopes to become a doctor one day, Micah is grateful to the researchers who strive to find cures: “Those medicines save kids’ lives and one of them saved mine.” This fund honors Micah’s cancer journey and supports neuroblastoma research to find better treatments and cures for kids with this disease.

There is a great need for new therapies for pediatric acute myeloid leukemia (AML), both to improve cure rates and to decrease toxicities of the current standard of care, which includes intense chemotherapy and often bone marrow transplant. Chimeric antigen receptor (CAR) T cells represent one such opportunity to improve care for these patients, especially given the success of CAR T cells in patients with other types of leukemia and lymphoma. Dr. Richards and colleagues have identified a protein called CD93 as a potential target on AML cells, and have generated CAR T cells that are specific for this target. Preliminary data show that these cells meet criteria for an effective CAR and show promise for potential translation to patients in the future. Dr. Richards is focusing on extending the initial testing of these CAR T cells to determine efficacy in treating leukemia in pre-clinical models and evaluating for possible toxicities as we consider the possibility of moving this therapy toward clinical trials in the future.

More frequently than previously recognized, children with leukemia have inherited mutations that make them likely to develop these cancers. These inherited syndromes are called leukemia predisposition syndromes and manifest with abnormalities in the bone marrow or leukemia. Recent studies have shown that these syndromes may account for over 10% of pediatric and young adult leukemia and the mutations in these patients may differ from adults with similar disease. Once leukemia develops in such patients, survival rates are drastically reduced, so many patients undergo painful and stressful annual bone marrow exams to monitor for leukemia. Major barriers to improving outcomes for these patients include: lack of markers for risk stratification, limited understanding of why these mutations lead to cancer and lack of understanding of why these patients have leukemia that is harder to treat. To better understand how disease-causing mutations arise in pediatric patients, Dr. Kennedy is analyzing genetic sequences from patients with a predisposition syndrome. These studies may be able to be performed on peripheral blood, sparing children bone marrow biopsies. Ultimately, she hopes that these studies will identify novel ways to monitor and treat pediatric and young adult patients at high risk for leukemia.

Osteosarcoma (OS) is the most common malignant bone tumor in children, but only five chemotherapy drugs have been shown to be beneficial, and overall survival remains poor (60%). There are no effective standard-of-care therapies for patients who relapse. Identifying new treatment strategies in OS is of paramount importance. Prior studies evaluating the genetic code of OS tumors show significant genetic heterogeneity among patients and have not uncovered recurrent changes that can be successfully targeted. Dr. Pavisic is using computational algorithms established by the Califano laboratory to identify universal tumor dependencies known as master regulator (MR) proteins from the messages expressed by the tumor’s genetic code to make proteins (RNA). Using information from drug studies done in OS cells, she is prioritizing drugs by their ability to reverse the activity of a tumor’s most aberrantly active MR proteins. MR proteins integrate the effects of many genetic alterations and are critical to tumor cell survival, thus represent novel tumor biomarkers and drug targets. Dr. Pavisic hypothesizes that MR analysis in OS will lead to biologically-relevant patient classification and risk stratification, and prioritize new drugs for immediate testing in laboratory models of OS and in clinical trials to improve outcomes for children with OS.

Clinical trials have been essential to the great progress that has been made toward curing childhood cancer. New personalized therapies in current clinical trials promise to be more effective and less toxic than drugs in the past. But, to truly understand what a child finds most bothersome and provide the best quality of life possible, we need to ask the child directly. No one has done this for children receiving personalized therapies for cancer that has returned or not responded to chemotherapy, a group where quality of life is especially important. To answer this question, a team from Seattle Childrens Hospital/University of Washington and Boston Childrens Hospital/Dana Farber Research Institute designed this study. Dr. Steineck and colleagues are using surveys, especially made for children, to learn what children feel when they are treated on a clinical trial and what bothers them the most. This will help doctors find better ways to recognize and treat these symptoms, alleviate suffering, and improve how children view their quality of life. Knowing this is important for families to understand what their child may experience with treatments used on todays clinical trials and guide them in their very important, but difficult decision about the care their child receives.

This grant is funded by and named for Friends for Hope, a St. Baldrick's Hero Fund created to honor Morgan Loudon and celebrate her strength and determination as a cancer survivor. Morgan was 9 years old when she was diagnosed with a rare rhabdoid tumor and today she has no evidence of disease. With this fund, the Loudon family hopes to rally family and friends to “battle on” in the search for cures and better treatments.
This grant was awarded at Seattle Children's and transferred to Medical College of Wisconsin.

Diffuse midline gliomas (DMGs) are aggressive brain tumors in children that are almost uniformly fatal. Curative surgery is not possible, radiation therapy provides only temporary relief, and chemotherapies have proven wholly ineffective. New, effective therapies are desperately needed for children with these tumors, but decades of clinical trials have so far failed to improve outcomes. Researchers have now identified a specific mutation (H3K27M) that affects how DNA is organized and drives a majority of DMG tumors. This insight has yet to result in new treatment options, however, an emerging understanding suggests that other cellular changes are required for tumors to grow. As the Kids Shouldn't Have Cancer Foundation St. Baldrick's Fellow, Dr. Dahl and colleagues have identified a protein complex called the SEC that DMGs with the H3K27M mutation are dependent on for survival. This complex regulates how DMG cells read their genetic code. An existing class of drugs called CDK9 inhibitors are effective in blocking the activity of the SEC. Dr. Dahl is researching how the SEC acts to promote DMG cell growth and testing whether CDK9 inhibitors can be used to interrupt this process. If successful, this research will provide the rationale for the design of future clinical trials using CDK9 inhibition as a new way of treating this intractable disease.

The Kids Shouldn’t Have Cancer Foundation, a St. Baldrick's partner, was founded after Jon and Kimberly Wade lost their son, Jonny and twin to brother, Jacky to medulloblastoma. He endured countless surgeries and procedures, pain and fatigue yet maintained unshakable faith and grace through it all. As a result, he told his mother, “I don’t want any other kid to have cancer.” Their mission is to honor Jonny’s wish by conquering pediatric brain cancer through research and political action with an emphasis on responsible spending.