Grants Search Results

ALL is the most common blood cancer occurring in children. Great strides have been made in the treatment of this disease, but new less toxic therapies for high risk ALL are needed. A new effective therapy is chimeric antigen receptor T-cells (CAR-T) which involves altering a patient’s own cancer fighting cells (T-cells) to express a protein able to recognize a protein on ALL cells (CD19), thus promoting killing of ALL cells. This form of therapy is much less toxic than traditional chemotherapy, but it is still associated with unwanted side effects. Dr. Falcon is working on ways to eliminate anti-CD19 CAR-T if severe side effects occur. This will greatly enhance the safety of this promising treatment.

A portion of this grant is generously supported by the Not All Who Wander Are Lost Fund, a St. Baldrick's Hero Fund which was named after Kiersten Dickson’s favorite quote from J.R.R. Tolkien and honors the memory of a free spirited, courageous young woman who battled a rare, incurable cancer. This fund hopes to advance cutting edge immunotherapy treatments for pediatric cancers.

A new class of drugs called EZH2 inhibitors is currently in clinical trials for the treatment of patients with relapsed B-cell lymphomas, a common subtype of pediatric lymphoma. These drugs suppress the activity of the EZH2 enzyme, which is known to be critical to tumor growth. Over time, however, if the lymphoma cells become resistant to EZH2 inhibitors, they may lose their effectiveness. Dr. Gulati aims to understand the mechanisms through which lymphomas develop resistance to EZH2 inhibitors. This will extend the usefulness of these drugs and will help in the development of methods to overcome the resistance. Awarded at the Memorial Sloan Kettering Cancer Center, and transferred to Baylor College of Medicine.

Based on progress to date, Dr. Iglesias was awarded a new grant in 2019 to fund an additional year of this Fellow award. Neuroblastoma is the second most common pediatric solid tumor. Patients with high-risk disease have only a 50% chance of survival. The immune system can be engineered to efficiently kill cancer cells while sparing healthy tissues. However, neuroblastoma has been shown to evade these treatments by downregulating their target structures and upregulating inhibitory proteins. Dr. Iglesias is developing immune cells that specifically recognize neuroblastoma cells and also circumvent the aforementioned treatment evading mechanisms by restoring the target structures and blocking the inhibitory proteins. Through this work Dr. Iglesias aims to develop a new treatment approach for patients with high-risk neuroblastoma.

Based on progress to date, Dr. Jones was awarded a new grant in 2019 to fund an additional year of this Fellow award. Patients with acute myeloid leukemia (AML) that is associated with a specific type of mutation in a protein called FLT3, have a poor prognosis. When these patients relapse, they have been found to have a unique mutation in this protein that makes their leukemia very difficult to treat. Dr. Jones is studying the effects of a novel FLT3 inhibitor in patients who have developed exquisitely resistant AML.

Children who have leukemia (a type of blood cancer) that is difficult to treat with just chemotherapy can be treated and even cured with transplants of blood stem cells from a donor. However, even when donor and patient cell types are carefully matched, immune system incompatibilities between a patient's body and cells from a donor can cause many complications including graft-versus-host disease, which can be fatal in extreme cases. Results from this research will hopefully teach us a way to manipulate the immune system using something called "exosomes" so that the child receiving the stem cell transplant is less susceptible to attack from the donor's cells and can have a successful cure. Through this research Dr. Kim hopes to be able to use exosomes to protect the child's body from the donor cells that can cause harm, yet preserve the donor cells that can fight the leukemia.

Based on progress to date, Dr. Koldobskiy was awarded a new grant in 2019 to fund an additional year of this Fellow award. Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Despite dramatic improvements in treatment outcome in recent decades, relapsed and resistant disease remains a leading cause of childhood death from cancer. Dr. Koldobskiy studies the ways in which leukemia cells rely on "epigenetic" modifications, or chemical marks that modify the expression of genes without a change in the genetic sequence itself. Variability of epigenetic marks allows leukemia cells flexibility in turning genes on and off, and may account for resistance to treatment. By dissecting the mechanisms of epigenetic modification in childhood ALL, he aims to identify new targets for treatment.

Based on progress to date, Dr. Pierro was awarded a new grant in 2019 to fund an additional year of this Fellow award. While outcomes for childhood leukemia have improved dramatically, the prognosis for children who relapse remains poor making relapsed leukemia one of the main causes of cancer death in children. Discovering the underlying pathways that lead to chemotherapy resistance and relapsed disease is therefore a top priority. To prevent relapse and improve treatment response, Dr. Pierro's laboratory has focused on discovering genetic mutations responsible for relapse and chemotherapy resistance. Mutations in a gene known as MMSET have been identified as one of the most common mutations in relapsed leukemia in children. This mutation in other cancers imparts a poor prognosis which suggests it has a role in drug resistance. Dr. Pierro's team has developed leukemia cell lines with and without the MMSET mutation and is treating the lines with chemotherapy to test this theory. He is also identifying the pathways controlled by this gene to identify the mechanism by which it protects the cells from the effects of chemotherapy. This information could be used to develop targeted therapy to prevent relapse and restore sensitivity to chemotherapy thereby improving outcomes.

Based on progress to date, Dr. Winger was awarded a new grant in 2019 to fund an additional year of this Fellow award. The goal of this project is to test a promising new drug called PLX9486 to treat pediatric cancers. In some cancers, a protein called "KIT" acts as an engine to drive growth. In comparison to existing treatments, PLX9486 is able to stop KIT in a unique way. Therefore, it is expected that this new drug will be very effective against cancers that are driven by KIT. However, over time cancer cells figure out ways to bypass drugs, leading to drug resistance. In addition to testing the effectiveness of PLX9486 against cancer cells, Dr. Winger is also studying how KIT might bypass the drug to develop resistance. Understanding the potential causes of drug resistance will allow her to develop strategies to overcome this resistance. This project will systematically evaluate a new drug that has the potential to transform the treatment of pediatric cancers driven by KIT.

Based on progress to date, Dr. Winters was awarded a new grant in 2019 to fund an additional year of this Fellow award. Dr. Winters' research involves developing more effective and more targeted therapies for children with acute myeloid leukemia (AML), a type of leukemia that continues to have poor outcomes. The therapy for pediatric AML has not changed much in 20-30 years, and many children who receive this therapy relapse. There is a protein on many AML cells called CD123, which marks the earliest leukemia cells. In adults there are drugs that target this protein which are being studied in clinical trials. However, no one has studied whether CD123 is a useful target in pediatric AML. Dr. Winters is looking at CD123 protein expression in AML samples from pediatric patients, as well as investigating whether expression of CD123 marks the primitive leukemia cells in these patients - that is, those that give rise to the leukemia and cause relapse. She is also testing some of the same drugs that are being used in adult clinical trials on these pediatric samples in a laboratory setting, to see if they may be useful in pediatric patients. These studies are expected to generate new therapy options for children with difficult-to-treat AML.

Based on progress to date, Dr. Wulff was awarded a new grant in 2019 to fund an additional year of this Fellow award. Ewing sarcoma (ES) is the second most common bone cancer in children. Approximately 25% of children with ES have metastasis, which are tumors that have spread to other parts of the body, such as the lungs. It is especially difficult to treat these children and more than 70% die within 5 years. Therefore, it is important to learn about what it is that allows these tumors to spread and hopefully develop new drugs to treat these patients. Certain proteins are expressed at much higher levels in metastatic lung tumors compared to the primary bone tumor, suggesting that these proteins play a role in allowing the tumor to spread. Dr. Wulff is studying the role of these proteins by increasing or decreasing them, and then testing how this affects the cancer's ability to grow and spread. Dr. Wulff's team thinks that the cancer's ability to spread can be decreased by decreasing a particular set of proteins. In addition, she is testing new drugs that inhibit the function of these proteins, with the hope to identify new therapies that will improve overall survival rates for patients with metastatic ES.

This is grant is generously supported by Team Clarkie, a St. Baldrick's Hero Fund. Clarkie Carroll was diagnosed with Ewing sarcoma in his upper right femur in 2013. He endured surgery and treatments with strength, positivity and a sense of humor. Today he has no evidence of disease.

A portion of this grant was also funded by this Hero Fund. It was created to honor Clarkie and ensure researchers have the resources to further Ewing’s sarcoma research as well as stimulate greater awareness and inspire others to believe pediatric cancer research can and will lead to a cure.

Based on progress to date, Dr. Mulama was awarded a new grant in 2020 to fund an additional year of this Scholar grant. Kaposi sarcoma-associated herpesvirus is a virus that causes cancer known as Kaposi sarcoma, which is very common in HIV+ children, especially in Africa and sometimes in individuals who get an organ transplant. Dr. Mulama is designing and testing a vaccine that prevents and treats the viral infection, as well as antibodies to detect infection in people. He will also test the vaccine so that one day it can be used as a treatment to prevent Kaposi sarcoma-associated herpesvirus infection and Kaposi sarcoma in more than 40,000 patients worldwide each year.

Neurons are nerve cells that populate certain regions of the human body and are responsible for transmitting chemical signals back and forth to the brain to regulate critical bodily functions. A deadly form of pediatric cancer, known as neuroblastoma, occurs when a subset of these neurons start to proliferate uncontrollably. These cancer cells can migrate and spread throughout the body, making it very challenging to treat with currently available drugs. This highly aggressive form of neuroblastoma occurs in children who are older than 18 months. At such an early age, this disease can be quite devastating and there is an imperative need to better understand how this form of neuroblastoma develops. Recent work has identified pediatric cancer mutations in distinct specialized proteins that regulate chromatin (the complex of DNA and proteins), known as chromatin remodelers. One such protein, ATRX, was recently found to be mutated frequently in neuroblastoma tumors identified in adolescent and young adults, which have poor overall survival. Dr. Bernstein is exploring a novel therapy for neuroblastoma patients that harbor ATRX mutations thorough innovative and state-of-the-art approaches. Dr. Bernstein's team is comparing the cellular changes that occur in the presence of the drug in models of neuroblastoma.

Many cancer treatments kill both normal and cancer cells. Drugs used in standard cancer treatments have long term effects in children, such as causing developmental delays or second cancers later in life. Dr. Blackburn's team is working to find new drugs that kill cancer cells, but do not affect normal cells. By discovering characteristics that are unique to cancer and finding a drug that recognizes that specific characteristic, they will be able to selectively kill cancer cells. Their research goal is to improve cancer treatments so that children can live long, normal lives after their cancer is cured.

Children with cancer continue to succumb to their disease, many after receiving toxic therapies like chemotherapy and radiation. Also, surviving children face life long negative health consequences ranging from learning disabilities, to more severe effects such as a higher chance of getting another cancer in adulthood. Therefore, additional, rigorous scientific research needs to be performed to develop new and effective treatment options for these kids. Cancer growing inside the body hides in plain sight of the immune system. This is because cancer cells evolve to escape recognition by the immune cells. Therefore reawakening the immune system could be a very effective way of using a patients' own attacker cells to engulf cancer cells and get rid of the disease. Dr. Davare is working to discover and test new ways to reactivate immune cells for attacking cancer cells. For this project, she has developed an innovative method to identify synthetic molecules that will uncloak the cancer cell and make it visible to the immune system for destruction. This research strategy, in the long run, will open new doors and has the potential to not only increase survival of children with cancer, but their long term quality of life as well.

This grant is named for Hannah’s Heroes, a St. Baldrick’s Hero Fund created in honor of Hannah Meeson and pays tribute to her fight by raising awareness and funding for all childhood cancers because kids like Hannah “are worth fighting for.”

The goal of this study is to develop new therapies for Ewing sarcoma by targeting a protein called EWS-FLI1. Many people believe that the key to improving outcomes for Ewing sarcoma patients is to develop new drugs that block EWS-FLI1. In order for this to be successful, there is a need to understand exactly what happens to the Ewing sarcoma cell when EWS-FLI1 is turned off. Dr. Grohar is using the latest technology to both characterize the consequence of EWS-FLI1 silencing and identify novel compounds that turn EWS-FLI1 off.

Acute myeloid leukemia (AML) is a cancer of the immature cells in the bone marrow. One common chromosomal abnormality found in pediatric AML is the inversion of chromosome 16 (inv(16)). Current treatments for inv(16) AML are associated with significant toxicity, as well as serious long-term chronic effects. Therefore, there is a pressing need to develop new, more targeted treatments for children with inv(16) AML. Inv(16) generates a fusion gene called CBFB-MYH11. CBFB-MYH11 causes changes in gene expression, which are the first step in the development of leukemia. Because Cbfb-MYH11 is expressed in all inv(16) leukemia cells, it makes an attractive drug target. Currently, there are no CBFB-MYH11 inhibitors suitable for use in humans. However, it is possible that other proteins cooperate with CBFB-MYH11, some of which may be better drug targets. One potential co-factor is HDAC1. Dr. Hyde's team found that HDAC1 binds CBFB-MYH11 and is required for its activity. They also found that an HDAC1 inhibitor significantly blocks the growth leukemia cells in culture. In this project, Dr. Hyde is testing whether HDAC1 is an important co-factor of CBFB-MYH11 and if HDAC inhibitors effectively target Cbfb-MYH11+ leukemia cells in vivo. These results will have direct clinical implications for children with inv(16) AML.

Ewing Sarcoma is an aggressive disease affecting children and young adults. Patients are treated with intensive chemotherapy. This helps some, but not all, with early disease, works poorly in those with advanced disease, and can have serious side effects. Searching for new and better therapies, Dr. Jedlicka's lab has found a new protein that works abnormally in Ewing Sarcoma and that could be a new target for treatment. Dr. Jedlicka is working to understand more about how this protein works and how best to block it, to see if it could be a useful new treatment.

Synovial sarcoma is a soft-tissue cancer in adolescents and young adults. More than half of patients develop metastasis, or spread of the cancer to the lungs. Once it has metastasized, synovial sarcoma is fatal in nearly all patients. Dr. Jones' team has developed a model of synovial sarcoma and found that when the tumor spread to the lungs many white blood cells begin to infiltrate the tumors. He is studying whether these particular white blood cells from the immune system are trying to fight the tumor or are helping the tumor grow and spread to the lungs. This team is testing if the presence of these immune cells in a large panel of human synovial sarcomas are associated with the same patients developing clinical spread of disease.

Adolescent and young adult (AYA) cancer survivors have an elevated risk of medical problems that can impact the quality and length of their lives, but few studies have focused on the occurrence of late medical conditions in this population. Using data on nearly all AYA cancer survivors in California, the Rich and Weissman Family Lymphoma Survivorship Fund St. Baldrick's Research Grant is identifying how often specific late medical conditions occur and how the risk of these medical conditions vary by clinical and patient factors. The results of the study will identify subgroups of young patients at increased risk of serious medical conditions, information critical to improving survivorship care and outcomes. Jared Weissman is a Hodgkin’s lymphoma survivor thanks to a clinical trial made possible by research. This Hero Fund honors his survivorship and his grandparents, Terri and Barry Rich, by funding research for new treatment options for cures and less toxic after effects for survivors.

Diffuse intrinsic pontine glioma, also referred to as brainstem glioma, is a pediatric cancer that accounts for the majority of deaths from brain tumors in children. Although radiation therapy is the standard of care for brainstem gliomas, the median survival of children with this tumor type is less than one year from diagnosis. In order to improve the treatment of these patients, Dr. Kirsch's team is using a model of brainstem glioma that can be used to evaluate the effectiveness of new therapies. Using this model, they are testing whether removing a protein called ATM, which is the target of drugs now entering clinical trials, will enhance radiation sensitivity in brainstem gliomas. They hypothesize that deleting this target, when given in combination with radiation therapy, will increase the number of tumor cells killed by radiation and will therefore improve survival in brainstem gliomas when they have a specific gene mutation commonly found in this childhood brain tumor. If successful, these studies will inform the design of future clinical trials testing this strategy in children with brainstem gliomas.

This grant is named for Hannah’s Heroes, a St. Baldrick’s Hero Fund created in honor of Hannah Meeson and pays tribute to her fight by raising awareness and funding for all childhood cancers because kids like Hannah “are worth fighting for.”