Grants Search Results

Young children with Down Syndrome are at very high risk of developing cancer of the blood (leukemia) before the age of 4. These leukemias arise from abnormal blood cells that are first detected in newborns with Down Syndrome. Studies suggest that the abnormal blood cells arise in the early embryo before a permanent blood system is set up. Dr. Palis has developed a unique way to study the biology of these abnormal blood cells. Researchers can now study the path from abnormal blood cell to leukemia in a dish. Using this system, he will learn how certain genes drive the change from 'abnormal blood cell' to 'cancer blood cell' that occurs specifically in very young children with Down Syndrome. Long-term goals are to prevent leukemia from forming and to develop safer treatments for those children with Down Syndrome who develop leukemia.

Neuroblastoma is a pediatric cancer that originates from mistakes in nerve cell development. Limitations in our mechanistic understanding of disease onset and progression have led to inaccurate patient risk predictions and over-treatment of infants, with long-term side effects. Recently, Dr. Kulesa and colleagues developed a computational model to predict neuroblastoma disease outcome based on a network of six development genes of receptor tyrosine kinase signaling that is more accurate at early disease stages than any current gene list algorithm. What remains to be determined is whether this model can be refined to increase its predictive value and tested to simulate hypothetical treatment strategies with individual patient data. To address these questions, he will include MYCN into the network model, a proto-oncogene gene that is correlated with poor prognosis, and compare model and experiment results of network perturbations that simulate targeted treatments. Dr. Kulesa will take advantage of acquired human neuroblastoma cell lines and our ability to modulate these genes in culture, and patient data from large-scale neuroblastoma genomic databases and published studies. At the conclusion of our study, he will have a better understanding of the mechanistic basis of neuroblastoma disease progression and a refined computational model to more rapidly and accurately predict individual patient disease outcome.

Rhabdomyosarcoma is a common cancer in kids. It can be a very aggressive disease, especially a type that is caused by a genetic change that creates an abnormal cancer-driving protein in the cell, called "P3F". P3F-driven rhabdomyosarcoma shows a strong tendency to spread to other parts of the body, which is what typically leads to death from the disease. P3F is a very hard drug target. However, P3F works together with other machinery in the cell to cause rhabdomyosarcoma. Such machinery could be targeted to interfere with P3F effects, but is not well understood. Dr. Jedlicka and colleagues have recently found new parts of this machinery that help P3F cause rhabdomyosarcoma to spread to other parts of the body. In this project he will better understand how this new machinery works and how it could be targeted to interfere with rhabdomyosarcoma spread. This work could identify new ways to inhibit the aggressive nature of this disease and improve patient outcomes.

This grant is generously supported by Marlee’s Smile, a St. Baldrick's partner, founded in honor of 12-year-old, Marlee Pack. Diagnosed with alveolar rhabdomyosarcoma; she relapsed three times in four years. After the final relapse, Marlee had to make a decision no child should have to: continue painful, toxic treatments or enter hospice care. She passed away on February 23, 2019. Our mission at Marlee’s Smile is to change the lives of kids with cancer, one smile at a time in two ways. We give a custom Build-A-Bear to every child fighting cancer, as well as their siblings to honor Marlee’s giving heart as she knew the comfort of a furry friend. We fund targeted research of pediatric cancers, specifically sarcomas to honor Marlee’s dying wish that no child should have to suffer the pain and hopelessness of current cancer treatments.

Pediatric high-grade gliomas (pHGGs) are a fatal childhood cancer of the brain. Deregulation of specific histone modifications, both with and without a direct link to specific mutations, have been identified in these tumors. This project will investigate histone H3 post-translational modifications (PTMs) in pHGGs to advance our understanding of tumor development and understanding of biologic characteristics, and to promote the identification of effective therapies for improving the outcomes for patients with these tumors.

This grant is generously supported by The Benicio Martinez Fund for Pediatric Cancer Research, a St. Baldrick's Hero Fund created in honor of Benny's fight with cancer and supports cures and better treatments for kids like him. 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. Since then he has had brain surgery, radiation and chemotherapy. Despite complications from treatment and setbacks, Benny has an amazing can-do attitude and is battling the cancer with courageous determination.

Dr. Resnick's research project focuses on how to cure one of the deadliest brain tumors in children called diffuse midline gliomas (DMGs), previously also known as diffuse intrinsic pontine gliomas (DIPGs). No available cancer treatments work against DMGs and children die from this lethal disease within 8-11 months of diagnosis. To improve survival and develop better treatment against DMGs, he assessed genes being turned on or off in DMG tumor cells. Together with colleagues, he has identified novel gene products common in multiple DMG tumors that arise when two unrelated genes join and become expressed as one novel protein entity. Here, he will study the role of these gene products, or gene fusions, in DMGs, specifically those involving a known cancer-causing gene called MET. He will test drugs that target the MET gene fusions in DMGs by performing experiments on models that accurately represent human DMG tumors. The results from this project will help identify new drug treatment strategies to target DMG tumors in children. Successful therapy options from this study will be made available to children with DMGs in real-time through our partnership with a clinical trial consortium that brings new treatments to children with brain tumors.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in childhood. Despite intensification of aggressive therapy involving combination chemotherapy, radiation and surgery, the overall outcome of RMS is among the least improved in childhood cancer. Dr. Huang and colleagues aim to explore a novel concept of applying a clinical available technique of tumor-reduction cryoablation, whereby tumors are damaged by ultra-cold argon gas or liquid nitrogen to release endogenous immune adjuvants, to enhance an efficacious systemic anti-tumor immunity against distant RMS metastasis. He seeks to procure preclinical efficacy and mechanistic data that will enable a rapid translational clinical trial targeting metastatic sarcoma within 3 years.

Alveolar rhabdomyosarcoma is one of the most aggressive and difficult to treat tumors in children. If not caught early, metastatic disease has a dismal 5-year survival of less than 5%, even after the most intensive chemotherapy possible. Even in the rare circumstances when these children do well, the long-term side effects of the intensive chemotherapy are debilitating. We can, and must, do better. We have known for some time that the cause of alveolar rhabdomyosarcoma in 60% of the most aggressive cases is a specific genetic abnormality. This genetic mistake creates a new gene, and Dr. Hiebert will determine how this new gene causes cancer and determine what would happen to these sarcoma cells if we had a drug specific for this new gene. To do this, he has engineered alveolar sarcoma cells grown in the lab so that this cancer gene can be quickly turned off by an existing drug. This allows, for the first time, the treatment of these sarcoma cells with a specific drug to define all of the events that occur in the first few minutes to several days of drug treatment to establish that inhibition of this new cancer gene is a viable therapeutic strategy.

This grant is generously supported by Rachael Chaffin’s Research Fund, a Hero Fund created in memory of a young girl who loved life. Rachael loved people, animals and the outdoors. It was heartbreaking when she was diagnosed with Rhabdomyosarcoma in the summer of 2013 at the age of 11. With a positive attitude and determination, Rachael began her long battle with cancer. She truly believed she would beat cancer so she could go on to help others. In 2014, Rachael organized a team of family and friends called “Kicking Cancer with Ray Ray” to raise funds for St. Baldrick’s and they continue the tradition today. This Hero Fund honors Rachael’s passion to find a cure for kids’ cancer and carries on her legacy of increasing awareness of childhood cancer to find better treatment options and cures through research.

For a child is diagnosed with a diffuse intrinsic pontine glioma so called DIPG, the options for treatment are scarce and so are the chances for survival. This aggressive brain tumor generally strikes children who are 6 years old and younger, with most surviving less than a year after diagnosis. The only known effective treatment is the use of radiation. Yet, even with radiation therapy most children show tumor progression within the year after radiation therapy. Given this reality, there is a desperately need to identify the drug that increase the anti-tumor activity of radiation, as a mean to improve treatment outcome for these children. DNA damage is thought to be the most toxic effect caused by radiation, and Dr. Hashizume and others showed that the majority of the DNA damage caused by radiation are repaired within 24 hours of treatment. This DNA damage repair is possibly responsible for the tumor progression observed in DIPG after radiation therapy, thereby ultimately taking no survival benefits to the patients. As the recipient of the Just Do It...and be done with it St. Baldrick's Research Grant, Dr. Hashizume recently performed a genetic screening in DIPG cells collected from patient tumor and found specific therapeutic targets which is important for DNA damage repair. This research will study whether targeted inhibition of DNA damage repair increase DNA damage by radiation, leading to increased radiation toxicity in DIPG. Successful results from this research will find a new effective therapy which increases the anti-tumor activity of radiation, in turn, will ultimately leads to improved treatment outcomes for children with highly malignant and currently incurable cancer.

This grant is funded by and named for the “Just Do It…and be done with it” Hero Fund created in honor of Sara Martorano who was 4 when she was diagnosed with Stage IV Wilms tumor. Despite a grueling treatment protocol of surgeries, radiation and chemotherapy, Sara didn’t let anything dim her sparkle. Thanks to life-saving research, today she is cancer free. This fund celebrates the courage of all cancer kids enduring treatment and the support of their family and friends.

Awarded at Northwestern University and transferred to Ann & Robert H. Lurie Children's Hospital of Chicago.

As the recipient of the Jack's Pack - We Still Have His Back St. Baldrick's Research Grant, Dr. Eischen is focused on researching Burkitt lymphoma, a blood cancer that predominately develops in children and young adults. The goal of this proposal is to investigate a novel approach to eliminate Burkitt lymphoma cells, and particularly difficult to treat relapsed and refractory to treatment Burkitt lymphoma. Although five-year survival rates for Burkitt lymphoma is 85-90%, treatment is toxic with associated complications, and children that relapse or that are resistant to treatment have poor survival rates even with additional therapy. Therefore, more research and new treatments are needed for Burkitt lymphoma. This project stems from a paradigm-shifting discovery she recently made and will use an innovative approach that includes testing newly designed compounds to target a specific protein called Mdm2 in Burkitt lymphoma cells causing their death. This approach should also cause the death of Burkitt lymphoma cells that contain mutations in a gene that make them resistant to many current therapies and that reduces patient survival. Completion of the research will result in increased understanding of the role of Mdm2 in human Burkitt lymphoma cell survival, testing of new compounds that target Mdm2, and pre-clinical tests with the compounds on human Burkitt lymphoma cells. The long-term goal of these studies is to have an improved, more effective treatment approach for non-Hodgkin's lymphomas, and particularly those lymphomas that are resistant to current therapies.

This grant is funded by and named for Jack's Pack - We Still Have His Back, a St. Baldrick's Hero Fund. Jack Klein was a ten 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.

The human immune system is astonishing in its ability to eliminate cells and organisms that give rise to disease. This process of immune surveillance is one of the last lines of defense that protect both adults and children from cancer; however, researchers have found that dysfunctional immune responses can permit cancerous leukemia cells to grow uncontrollably in the body. In this work, Dr. Dreaden will improve upon a drug that attempts to restore immune elimination to leukemia by redirecting a subset of immune cells, so-called T cells, to bind with and kill cancerous cells. By tethering such drugs with molecules that stimulate T cells to multiply, and possibly enable these cells to recognize leukemia cells again at a much later date, he aims to further improve both the strength and durability of responses to this promising class of immuno-therapy. Already, Dr. Dreaden and colleagues have made and screened more than 45 of these unique, multi-functional therapies and aim here to study the precise mechanics by these drugs act on immune cells, as well as their ability to impart memory-like immune responses to leukemia. Given the modular nature of this treatment approach, it could be rapidly extended to a range of other cancer cells, immune cells, and immune stimulating factors in the future.

Precise understanding of the basic mechanisms by which childhood cancers develop is essential to design tailored and superior treatments for cancer patients. These treatments are expected to cure and avoid long-term complications in cancer survivors. In many instances, we turn to models to reproduce human cancers, but the success of this strategy depends on how accurately we can unravel the origin of the disease. This project is based on Dr. Dominguez-Sola and colleagues recent findings on the origins and cellular basis of Burkitt lymphoma, a most aggressive form of childhood lymphoma with little treatment alternatives. This project will use unprecedented models of this cancer type to expand our understanding of the mechanisms of disease and identify therapeutic strategies that are less toxic, more effective, and superior to those currently available in the clinic.

This grant is funded by and named for Jack's Pack - We Still Have His Back, a St. Baldrick's Hero Fund. Jack Klein was a ten 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.

Pediatric cancers are often comprised of mixtures of cells with different characteristics. Some of the most important differences relate to chromosomal changes, with some cells having a normal or nearly normal chromosome profile, others having altered numbers of intact chromosomes, and yet others having extra or missing copies of one or more chromosome segments. Prior studies have shown that cancers with more segmental changes are usually more aggressive and therapy-resistant, but the specific effects associated with the different chromosomal changes are unknown. Here Dr. Cobrinik and colleagues will define the effects of such changes in two pediatric cancers -- retinoblastoma and neuroblastoma -- by isolating individual cells within the tumors that either have or lack specific chromosome changes, comparing their overall gene expression and cell signaling profiles, and identifying the critical changes that increase malignancy. The study involves three investigators with expertise in neuroblastoma, retinoblastoma, and a novel single cell sequencing approach that enables us to distinguish and characterize the chromosomally distinct cells within individual tumors in unmatched detail. This study is expected to reveal the most central features that distinguish more versus less aggressive cancers, as a critical step towards targeting and subduing the more aggressive and lethal cells within individual tumors.

Acute lymphoblastic leukemia (ALL) is the most common cancer of children, and although treatment is considered largely successful, in many cases leukemic cells stop responding to chemotherapy and re-emerge. As a consequence, ALL relapse remains a leading cause of childhood cancer-related death. Dr. Aifantis will test the possibility that the bone marrow microenvironment surrounding the leukemia supports the growth of disease and protects leukemia cells from chemotherapy. Together with colleagues he generated the first map of the ALL immune cell microenvironment allowing identification of novel players within the remodeled leukemic bone marrow that promote leukemia survival. They found that high levels of a specific cell type, known as non-classical monocytes, in ALL patient blood and bone marrow correlates with inferior patient survival. They demonstrated that depletion of leukemia-supporting monocytes enhances killing of leukemic cells with specific ALL therapies. In this project Dr. Aifantis will investigate the processes giving rise to monocytes capable of supporting leukemia survival. Further, he will use novel model systems to test whether targeting monocytes enhances responses to a range of existing ALL therapies as well as emerging approaches, such as Chimeric Antigen Receptor (CAR) T-cell therapy, that utilize a patient's own immune system to kill leukemic cells.

Ewing Sarcoma (EwS) is an aggressive bone and soft tissue tumor occurring in children and young adults. Approximately 25-30% of patients already have metastases at diagnosis and in spite of aggressive treatment, the survival for patients with metastatic disease remains dismal. EwS is considered an immune cold tumor that is largely resistant to conventional immunotherapy. Alternative treatment approaches are sorely needed, particularly in patients with metastatic disease. Dr. Sorensen and colleagues are using three novel strategies for targeting EwS tumors: 1) Inhibiting an EwS specific fusion protein that drives EwS tumor development. 2) Targeting a surface protein called IL1RAP. 3) Recruiting natural killer (NK) immune cells to EwS tumors and priming them to attack the tumor. This grant is the result of a generous anonymous donation to fund Ewing sarcoma research, specifically. It is in honor of a teenager fighting Ewing sarcoma, and is named the St. Baldrick's - Martha's Better Ewing Sarcoma Treatment (BEST) Grant for All.

Acute lymphoblastic leukemia (ALL) remains the most common cancer of children and young adults. Despite intensified treatments that achieved cure rates around 85%, there is a number of children who will relapse and succumb to therapy-resistant disease. One of the revolutions in the treatment of human cancer the last decade was immunotherapy, the ability of our own immune system to fight cancer. Unfortunately, despite its successes in a number of solid tumours, immunotherapy has not really impacted the treatment of leukemia, with the exception of CAR-T cell treatment of pediatric B-ALL. Indeed, some frequent types of pediatric ALL, and specifically T cell ALL (T-ALL) and its subtypes, have no immunotherapy treatment options. We believe that this is because we still don't understand how the cells of the immune system interact with the leukemia. Actually, researchers don't even know what type of immune cells are there available to fight the disease. Dr. Aifantis is applying a number of single cell techniques to create a map of the immune cells in the bone marrow of children with T-ALL. He is doing this at diagnosis of the disease, after treatment (remission) and when the children relapse. These studies will offer the first map of the immune system in pediatric ALL and will enable researchers to propose ways to activate the immune system to fight the tumour.

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.

Acute lymphoblastic leukemia (ALL) is the leading cause of cancer-related death in young people. The high-risk ALL is a subtype of ALL that fare a high rate of relapse and mortality. Intriguingly, high-risk ALLs show increased signaling response to growth factors that results in uncontrolled cell proliferation, a block in normal B cell development, as well as a loss of tumor suppressor genes. Currently, the field is hampered by a lack of models that closely resemble human high-risk B cell leukemia for discovery of novel therapeutic therapies. Dr. Tong has generated novel models that closely resemble human high-risk B cell leukemia that are amenable for downstream applications. She is now using these novel models to perform a genome-wide genetic screen to identify novel targets to eradicate B-ALL proliferation. Furthermore, she is working to discover druggable signaling pathways that confer resistance to existing ineffective therapies. Therefore, this work will likely provide new insights into therapeutic strategies in treating pediatric high-risk B-ALL.

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.

Pediatric acute leukemias are aggressive blood cancers that result in many childhood cancer deaths despite intensive treatments. Because these leukemias are highly sensitive to radiation, researchers have developed a technology called radioimmunotherapy. Radioimmunotherapy uses antibodies to deliver a radiation payload directly to cancer cells. Most existing radioimmunotherapies are directed against two cell surface proteins called CD33 or CD45. However, because these proteins are also found on many normal blood cells, the amount of radioimmunotherapy that can be safely given via CD33 or CD45 antibodies is limited.

As the recipient of the Emily Beazley's Kures for Kids Fund St. Baldrick's Research Grant, Dr. Walter is developing and rigorously testing a new form of radioimmunotherapy that is directed against CD123. CD123 is found on only a few normal blood cells but is heavily expressed on leukemia cells in most children with acute leukemia. Moreover, CD123 is particularly attractive as a target as it is widely overexpressed on underlying leukemic stem cells (the rare cells that have the ability to generate and fuel these cancers), whereas normal blood stem cells express little or no CD123. These studies are the first to test the value of CD123-targeting radioimmunotherapy and will guide researchers towards bringing this new, less toxic treatment to pediatric patients. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma. Her cancer was extremely aggressive, and she bravely battled it through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle. She inspired a community to come together to show love and changed lives with her message: “You gotta stay strong, you gotta stay positive, no matter what happens.” Emily passed away in 2015 at age of 12. She often talked about her dream of starting a foundation that funded research. She named it “Kures for Kids”. Her family and friends carry on her dream and her mission with this Hero Fund.

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.