Grants Search Results

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.

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.

Osteosarcoma is a cancer of bone that happens in young people. Dr. Davis and colleagues are trying to find ways to help the immune system fight off tumor cells, which may help us find a cure. They are examining all of the different type of immune cells in over 100 osteosarcoma tumor samples to identify how patterns in the cells match with other characteristics, such as how well a patient does with standard osteosarcoma treatment. They are also looking at biopsies from patients before and after immune therapy and will try to boost responses to immune therapy with a targeted drug. By understanding the way the immune system "sees" (or doesn't see) osteosarcoma, they will be able to predict which patients will benefit from different types of immune therapy and who will need other drugs added to their treatment regimen.

A portion of this grant is generously supported by the Sweet Caroline Fund, a St. Baldrick's Hero Fund, created to honor the memory of Caroline Richards who was diagnosed in 2014 with osteosarcoma in her right arm when she was 11 years old. She persevered through rigorous treatments with a giving spirit and a contagious smile, always thinking of how to make others happy or laugh. Caroline sadly lost her battle a year later but this fund pays tribute to her compassion for others by supporting osteosarcoma research to help kids with cancer.

Based on progress to date, Dr. Velasquez was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. Childhood acute myeloid leukemia (AML) is a blood cancer that is very difficult to treat in children and adolescents. T cells are one component of the patient's own immune system that helps defend against infections. New cancer treatments use modified T-cells that can ‘see' and kill cells that have CD123, a molecule present on AML, and have shown promising results in studies in the laboratory. Dr. Velasquez is testing if these specific T-cells are safe and can kill leukemia cells in children that have AML that came back after initial treatment. She also wants to see what happens to these T-cells after they have been given to the patient and how it affects the tumor. This information from the treated patients and the study of their T-cells and tumor cells will be useful in finding a cure for AML.

Survivors of cancer have a higher risk of health problems because of the severity of the chemotherapy and radiation treatments they received. As survivors of childhood cancer age, they increasingly succumb to the "late effects" of their cancer treatment (such as second cancers and heart and lung disease). After 10-15 years, these late effects become the leading causes of death in this population. Adolescents and young adults (AYAs, aged 15-39) are a subgroup of cancer patients that are defined as high risk because they: more commonly suffer from toxicities and side effects of their cancer treatment; have unique barriers to accessing health care; and suffer specific psychosocial concerns because of their life stage transitioning into adulthood. To date, little research has been done on the factors that influence long-term health outcomes in the population of survivors of AYA cancer. Dr. Moke is working to explore how cancer and its treatments affect health later on in life in survivors of AYA cancer, identify the causes of death in this population, and determine what factors and cancer treatments are associated with these specific life threatening health problems. This study will provide the baseline data needed to design ways to decrease the severity of and death from these late effects, and thus be an important step in promoting long and healthy lives in survivors of AYA cancer.

Surviving cancer is an achievement of immeasurable magnitude, however for most survivors this achievement does not signify the end of cancer related health issues. The cardiovascular system is commonly affected by cancer treatment and cardiovascular disease is the second leading cause of death in childhood cancer survivors. As the To-morrow's Research Fund St. Baldrick's Scholar, Dr. Bottinor is helping childhood cancer survivors live healthier lives by using advanced cardiac imaging techniques to identify survivors with subclinical cardiovascular dysfunction before they develop overt heart disease. She plans to use echocardiographic imaging to detect cardiovascular disease at its earliest stages, when treatment is most likely to be efficacious.

Dr. Bottinor is analyzing cardiac screening studies collected in routine care to determine if subclinical abnormalities can predict which survivors are at risk for subsequent cardiovascular disease and therefore the most likely to benefit from early medical intervention. She believes these techniques will be helpful in childhood cancer survivors because previous work in adult patients has suggested that advanced cardiac imaging techniques can predict which patients with cancer on active treatment are at higher risk for developing subsequent cardiovascular disease.

This grant is named for To-morrow's Research Fund, a Hero Fund created to honor Becky Morrow who is a childhood cancer survivor. Becky was diagnosed with acute lyphoblastic leukemia when she was 12 and endured grueling treatments and its side effects. Today she is cancer free, a wife and a mom but suffers late effects. This fund supports survivorship research for safer treatments that help kids not only survive but thrive.

Awarded at Vanderbilt University and transferred to Virginia Commonwealth University.

There is a type of leukemia which occurs mainly in infants, but also in children who have previously received chemotherapy for an unrelated cancer. This type of leukemia is extremely difficult to treat and often comes back despite chemotherapy. We have evidence that this leukemia relies on a protein called MBNL1. By disrupting MBNL1, leukemia cells cannot produce specific proteins they need to grow. As the Julia's Legacy of Hope St. Baldrick's Scholar, Dr. Lee, as proof of concept, has shown that MBNL1 can be blocked by a chemical inhibitor. By using computer models, testing large libraries of drug-like chemicals, and applying special chemistry techniques to improve how effective a drug is, Dr. Lee is looking for a way to block MBNL1 with a drug that can be used in humans. This will lead to a new therapy for this class of leukemias.

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

Based on progress to date, Dr. Stanton was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant.
Rhabdomyosarcoma (RMS) is a highly aggressive and lethal pediatric cancer affecting children and adolescents and arises in the soft tissue and skeletal muscle of the extremities, head and neck, and reproductive organs. From the clinical perspective, although patient outcomes have improved in general, nevertheless survival rates for some RMS tumors remains at less than 30%. One particularly aggressive subtype is alveolar RMS which is driven by the occurrence of chromosomal translocations resulting in the generation of chimeric or fusion proteins between the PAX3 or PAX7 and the FOXO1 genes. These are known as fusion-positive RMS (FP-RMS) and are associated with reduced relapse-free survival and generally poorer outcomes. But researchers still have limited understanding of how the "fusion" gene itself is driving the tumor, and no subtype-specific therapies exist. Dr. Stanton aims to determine how the fusion gene works with a protein complex known as BAF, to alter the epigenetic state of the cell to keep them dividing and stop the cell from differentiating into mature muscle tissue. His team is exploring the mechanism of how the BAF complex regulates the epigenetic state and memory of the FP-RMS. Furthermore, using small-molecule drugs and genetic depletion strategies (CRISPR) they will determine if FP-RMS tumors are dependent on the BAF complex for survival. Finally, they are working to identify potential novel therapies for patients with aggressive and lethal FP-RMS, to improve their outcome.

The 2021 and 2022 portions of this grant is funded by and named for the Aiden's Army Fund. When he was 8 years old, Aiden Binkley was diagnosed with Stage IV rhabdomyosarcoma. He had a huge tumor in his pelvis and the cancer had metastasized to his lungs. But this bright, funny and courageous boy believed he got cancer so he could grow up to find a cure for it. Aiden’s story has inspired so many people and his vision to cure cancer is being carried on by Aiden’s Army through the funding of research. They will march until there is a cure!

The 2020 and 2023 portions of this grant is funded by and named for by Berry Strong, a St. Baldrick’s Hero Fund, established in honor of Caroline Berry. Diagnosed with alveolar rhabdomyosarcoma when she was 14, Caroline endured a two-year battle with courage and determination. Throughout treatments of radiation and chemotherapy and undergoing six surgeries, Caroline was a beacon of hope, unselfishly raising awareness and funding for research so no child would have to endure what she did. After a brief remission, scans revealed Caroline had relapsed and she passed away on Thanksgiving in 2018. Caroline is remembered as a bright light, creative, intelligent, funny and feisty who was always eager to share a smile with others. She continues to be an inspiration through the Berry Strong Hero Fund which will continue her legacy and her passion to raise awareness and fund the most promising childhood cancer research.

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.

Dr. French is studying one of the most deadly childhood and adolescent cancers known, called NUT midline carcinoma. There is no effective treatment for this cancer, which has a median survival of 6.7 months. Recently, his team discovered a new class of drug, called 'NEO', that in preliminary studies appears promising in models, an unprecedented finding that gives some hope that they may have stumbled across a new effective treatment for this disease. Based on some recent studies, Dr. French thinks that the drug class directly acts against the cancer protein that drives NUT midline carcinoma, called BRD4-NUT. BRD4-NUT is created by a mutation that fuses one gene, BRD4, to another, NUT, which alone don't cause cancer, but when fused together create a very potent cancer protein. He think the drug inhibits both the BRD4 and NUT halves of this fusion in a manner that gives the drug some selectivity for BRD4-NUT. The findings are exciting because the NEO drugs are set for clinical trials to begin in 2019. Dr. French and colleagues are working to 1) validate the findings that the NEO drugs work well in models bearing NUT midline carcinoma to provide rationale to enroll NUT midline carcinoma patients onto these trials, and 2) determine scientifically how the NEO drugs inhibit NUT midline carcinoma growth.

Cancer associated with different types of lymphocytes is known as lymphoma. Different forms of lymphoma are a common cause of pediatric cancer in the US. Current clinical therapy is based on conventional chemo- and radiation therapy, which is associated with numerous side effects.

As the recipient of the Jack's Pack - We Still Have His Back St. Baldrick's Research Grant, Dr. Bahal is researching an alternative robust therapy against lymphoma by exploring new chemically modified therapeutic molecules and their interaction with novel targets. One of the major challenges associated with current therapies are side effects due to non-targeted delivery of the drug to the normal bystander cells that can result in potential toxicity. Dr. Bahal is using a nanotechnology based approach for targeted delivery. He aims to accomplish two specific goals: a) To optimize the design and synthesis of a new class of bioactive molecules to target pediatric lymphoma; and b) To test the therapeutic effect of synthesized molecules in disease-related models. Investigation of these novel methods will lead to the development of novel drug candidate for pediatric lymphoma. Jack Klein was a 10 year old who loved life, laughing and monkeys. During his illness, his community of family and friends near and far rallied around him under the moniker "Jack's Pack". Their slogan was "We have Jack's Back". After Jack succumbed to Burkitt's Lymphoma, his "pack" focused their energy and efforts to funding a cure...just as Jack would have wanted.

Malignant brain tumors are the most common cause of cancer-related death in children. The current standard of care treatment is often associated with lifelong cognitive and motor deficits and is almost inevitably followed by disease recurrence. Therapies that specifically and efficiently target tumor cells and minimize toxicity to normal cells are thus critical to the next generation of interventions that promise improved clinical outcomes for children affected by these deadly diseases. Capitalizing on our current knowledge of tumor metabolism and how metabolic pathways affect immune response, Dr. Deleyrolle is testing an innovative therapeutic modality based on reprograming the metabolic qualities of anti-tumor immune cells to enhance immunotherapy for childhood cancer. Successful completion of this project will demonstrate that immunometabolism represents a viable and critical target for the development of new cancer therapies to treat pediatric cancers, especially brain tumors. Dr. Deleyrolle is the recipient of the Pray for Dominic St. Baldrick's Research Grant. This grant is funded by the Pray for Dominic Hero Fund which was established in honor of an amazing boy who had so much joy and compassion for others even in a difficult battle with a rare and aggressive cancer. This fund carries on Dominic's legacy of joy and hope by funding research for high grade gliomas such as glioblastoma and DIPG for which there is no cure.

This grant is named for the Pray for Dominic Hero Fund. The fund was established in honor of Dominic Liples who lived with joy. He is remembered for compassion and determination while he faced his own difficult battle with a rare and aggressive brain cancer. The Pray for Dominic fund carries on Dominic's legacy of joy and hope by funding research for high-grade gliomas.

Outcomes for children with acute lymphoblastic leukemia (ALL), the most common pediatric cancer, are dependent on age, biological subtype, and early response to therapy. Survival for certain subgroups have improved by intensifying therapy. Patients with persistent leukemia after the first month of therapy have an increased risk of future relapse, regardless of underlying leukemia subtype or treatment protocol. Therefore, patients with even low levels of persistent leukemia receive intensified therapy to induce complete molecular remission prior to stem cell transplant, making therapeutic targeting of low level residual leukemia important in the frontline setting. However, the biological features of this minimal residual disease have not been assessed and therefore precision approaches are currently out of reach. Understanding the biology of residual leukemia has critical implications for ongoing therapy. Vulnerabilities specific to leukemia cells that have survived during the early phases can be an avenue for future clinical trials for this population of patients. The biology of these rare leukemia cells may also be a window into the broader dynamics of ALL eradication. Even in cases with great responses to induction therapy with no detectable disease, patients require years of therapy to reduce the risk of relapse, demonstrating the residual leukemia cells are present. Such undetectable residual leukemia likely has similar biology to low level residual leukemia. Dr. Alexander is combining proven clinical tools that carry rich prognostic information, with flow cytometry approaches to isolate rare leukemia cells, and to utilize novel genomic tools including single cell analysis to describe the biology of residual leukemia.

For children with pediatric brain tumors radiation therapy has been the backbone of treatment, in combination with surgery and chemotherapy. Although pediatric brain tumors can be highly responsive to radiation its use needs to be limited since radiation can be damaging to the brain, causing abnormal inflammation and long-term cognitive deficits that will profoundly impact the lives of patients. As the recipient of the Benicio Martinez Fund for Pediatric Cancer Research St. Baldrick's Research Grant, Dr. Sredni and her colleagues have identified a new drug (MW151) that can be given orally to patients receiving radiation therapy and can protect their brains against the cognitive decay caused by radiation. They are about to start a clinical trial, funded by the government (NIH/NCI), associating MW151 to whole brain radiation for the treatment of adults with brain metastases. Her goal is to move this approach to the pediatric population. This project is performing experiments that will test if inhibiting neuroinflammation with MW151 will interfere with brain tumor's response to radiation. This information is crucial to allow them to move forward with the studies necessary to use this protective drug in children. This new drug candidate has the potential to provide a safe and effective new adjunct protective treatment strategy. It can potentially transform the care and significantly improve the quality of life of our young patients and their families. 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.

Childhood leukemia patients diagnosed with MLL rearranged leukemia (MLL-r) have a particularly poor outcome. MLL-r cells are dividing endlessly, due to the constant growth signal sent by a protein located on the cell surface called FLT3. FLT3 signals can be regulated by chemically modifying the protein in a variety of ways. Dr. Li is exploring a novel way to regulate FLT3 by studying how the activity of FLT3 is regulated by PRMT1 mediated methylation, and evaluating whether a PRMT1 inhibitor in combination with the traditional FLT3 inhibitor could completely "turn off" survival signal of MLL-r leukemia.

Altering chemotherapy, including dose intensification, has not improved the survival for osteosarcoma (OS) patients. Genomic analysis has been unsuccessful in identifying consistent targetable options, and there were no responses in relapsed/refractory OS patients treated in numerous Phase I or II trials. Identifying new therapies is imperative. Immunotherapies such as dendritic cell vaccines (DCV) and checkpoint inhibitors have shown activity against adult cancers but there are no studies in children or adolescents (AYA) with OS. Dr. Kleinerman and colleagues demonstrated the efficacy of checkpoint inhibitor therapy against OS lung metastases. They have also showed that the activity of DCV can be improved by checkpoint inhibition. They are investigating whether a unique dendritic cell vaccine that augments T-cells is effective against primary and metastatic OS. This project aims to identify new therapeutic approaches for treating children and AYAs with relapsed/metastatic and primary OS. If efficacy is demonstrated, this approach can be translated into a clinical trial for children with OS lung metastases. Another goal is to combine vaccine therapy with chemotherapy for newly diagnosed patients to improve disease-free survival.

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.

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Although most children and adolescents are cured with modern treatments, relapsed/refractory ALL remains one of the most common causes of death from pediatric cancer. This observation highlights the importance of understanding why the leukemia cells of some children are difficult to kill with modern drugs (this is called intrinsic resistance). Glucocorticoids are a type of drug that have been used to treat ALL for over 50 years and are given to all children with ALL. It is known that it is harder to cure children with ALL when their leukemia cells show intrinsic resistance to glucocorticoids. He is now working to understand how IL7 makes ALL cells resistant to glucocorticoid drugs and to use this knowledge to develop ways to cure more patients. He has identified drugs that appear to suppress the effects of IL7 on ALL cells and that make them more sensitive to glucocorticoids. They believe that combining one of these drugs with glucocorticoids could cure more children with ALL in the future.

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.

Thanks to advanced diagnosis and treatment, many children now can be treated from cancer and stay alive for a long time; they are called survivors. Some anticancer drugs are harmful to the heart and may cause heart failure in these survivors. High blood pressure increases the risk of heart failure in survivors, but no one knows how this happens. Dr. Zordoky has developed a new model to answer this question. He thinks that anticancer drugs make the hearts age faster leading to a worse response to increased blood pressure. He is looking at a natural compound and a new group of drugs which prevent aging to see if they will protect the hearts from the bad effects of anticancer drugs and make the hearts stronger when hit by high blood pressure. The findings of this research will open the door for testing these compounds in the clinic in order to prevent late side effects of anticancer drugs in survivors.