Grants Search Results

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.

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.

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.

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.

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.

Doctors have been testing ways to boost the immune system to fight cancer in clinical trials over the last ten years. Although these approaches have led to very impressive results in patients with blood cancers, they have not worked well in patients who have tumors in their solid organs. Solid tumors have specialized cells that act as bodyguards, protecting the cancer cells from the immune system. Dr. Parihar has developed a strategy to selectively remove these 'bodyguard' cells from tumors, which will then allow the immune system to enter tumors and kill the cancer cells. He will test a new and selective nano-medicine he has created to kill 'bodyguard' cells. If successful, the new nano-medicine can help the immune system of patients with a range of childhood solid tumors, including neuroblastoma, one of the most common extra-cranial solid tumors in children where response rates remain low.

Dr. Rowe is applying stem cell biology to understanding childhood leukemia. Overall, pediatric oncologists have made remarkable progress in treating children with leukemia with chemotherapy, but some children have forms of leukemia that don't respond well. Dr. Rowe is interested in better understanding what makes this subset of leukemias resistant to treatment. To do this, he is developing new models of these unfavorable forms of leukemia so that he can understand precisely how normal blood cells become leukemic blood cells. If Dr. Rowe can achieve this, then researchers can find new ways to more effectively treat these forms of leukemia.

Over the past 10 years, we have made great strides in the diagnosis of Medulloblastoma, the most common malignant brain tumor of childhood. These advances have come from widely collaborative efforts to perform DNA sequencing on tumor specimens. This effort led to the identification of major subtypes of Medulloblastoma and a recognition that these subtypes are associated with differences in response to standard treatments and survival. Lagging behind, has been an understanding of the molecular mechanisms that drive relapse of Medulloblastoma. This occurs in 30-40% of Medulloblastoma patients and as yet, there are no curative options. As the recipient of the Thumbs Up Fund to Honor Brett Haubrich St. Baldrick's Research Grant, Dr. Rubin and his team members are proposing a novel clinical trial to address this pressing unmet need. Their trial, brings together what has been learned from sequencing Medulloblastoma and the recently developed ability to test the sensitivity of an individual patient's Medulloblastoma cells to hundreds of drugs simultaneously. The long-term goal is to use the combination of drug testing and DNA sequencing to design personalized treatments for relapsed Medulloblastoma patients. Success in this effort would not only provide new treatments for relapsed Medulloblastoma, but would also provide a new paradigm for personalized approaches to the treatment of all pediatric brain tumors.

A portion of this grant is funded by and named in honor of The Thumbs Up Fund to Honor Brett Haubrich, a St. Baldrick's Hero Fund. Brett is remembered for his kindness, his joy in making others happy and his faith even through his 3 ½ year battle with anaplastic astrocytoma, a difficult to cure brain cancer. Brett was diagnosed at the age of 11 and endured treatments and laser surgery which impacted his motor and speech functions. Yet he was always positive, often giving his signature “thumbs up” as a symbol of hope. In his honor, Team Brett began participating in St. Baldrick’s head shaving events in 2015 and each year, raised over $10,000. This Hero Fund hopes to raise funds for childhood cancer research for brain tumors like Brett’s so other families would have more options for cures.

The proto-oncogene MYCN is amplified in approximately half of patients with high-risk neuroblastoma. At relapse, tumors from high-risk patients typically activate a pathway called "MAP kinase signaling" through genetic mutations including loss of NF1, which normally dampens MAP kinase function. Since relapsed neuroblastoma is generally therapy resistant, these data suggest that MAP-kinase activation contributes to therapy resistance. Does MAP kinase signaling contribute to therapy resistance in MYCN-amplified neuroblastoma at diagnosis? Dr. Weiss proposes that dependence on increased MAP kinase signaling in MYCN-amplified neuroblastoma enables rare cells within this heterogeneous tumor to evade chemotherapy. This therapy-resistant population then undergoes selection for further activation of MAP-kinase signaling, reinforcing therapy resistance. How does MYCN drive MAP kinase? The NF1 tumor suppressor blocks MAP kinase signaling. Mis-splicing of the NF1 messenger RNA in neuroblastoma cells results in NF1-23a, a protein with decreased ability to block RAS. Inclusion of NF1 exon 23a is regulated by the RNA splicing proteins "T-cell intracellular antigen 1" (TIA1) and "TIA1 Like gene" TIAL1, both of which are MYCN target genes. If activation of TIAL and TIAL1 (TIA/L1) in MYCN-amplified neuroblastoma activates MAP-kinase signaling in primary tumors at diagnosis, does traditional treatment of these tumors select for further flux through MAP-kinase signaling, to enhance resistance at relapse? This is the issue that Dr. Weiss' proposal addresses. Successful completion clarifies the importance of MYCN-TIA/L1 axis as a driver of resistance in neuroblastoma, and suggests a a translational path to improve outcomes in neuroblastoma.

Dr. Weiss' grant is generously supported by the Arden Quinn Bucher Memorial Fund, a St. Baldrick's Hero Fund. Arden’s intelligence, empathy, and dynamic personality charmed everyone and is now her legacy. Before her neuroblastoma diagnosis on October 11, 2007 at age two, she happily played with boundless energy and imagination. Even throughout her difficult months of treatment, Arden bravely managed to keep smiling and learning. This fund supports St. Baldrick’s mission: funding the most promising research, wherever it takes place to provide kids fighting cancers less toxic, more effective treatments allowing them to live longer, healthier lives.

Therapies that only inhibit tumor cells but not normal cells are missing for the deadly childhood brain tumor medulloblastoma. As the recipient of the Miracles for Michael Fund St. Baldrick's Research Grant, Dr. Zhang has identified a promising drug target in medulloblastoma. This project aims to study the role of the target in medulloblastoma and evaluate the therapeutic potential of inhibiting this target using cutting-edge technologies and models.

This grant is funded by and named for the Miracles for Michael Fund, a St. Baldrick's Hero Fund created in memory of Michael Orbany who was diagnosed with medulloblastoma when he was 6 years old. After completing initial treatment, his cancer relapsed within a year and he passed away at the age of nine. Michael had unwavering faith and perseverance, wanting most of all to make others happy. This fund honors his tremendous strength to never ever give up.

The AACR-St. Baldrick's Foundation Award for Outstanding Achievement in Pediatric Cancer Research has been established to bring attention to major research discoveries to the pediatric cancer research community and to honor an individual in any sector who has significantly contributed to any area of pediatric cancer research, resulting in the fundamental improvement of the understanding and/or treatment of pediatric cancer. The recipient will nominate an emerging leader conducting research in the academic sector to receive a research grant. The 2020 SBF-AACR Award for Outstanding Achievement in Pediatric Cancer Research went to Dr. James Downing at St. Jude Children’s Research Hospital. Dr. Jarno Drost at Princess Maxima Center for Pediatric Oncology received the 2020 research grant. Dr. Drost's research interests are in Kidney and Rhabdoid Tumors.

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.

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.

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.

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.

Cancer remains a major cause of death in children. It is still difficult to collect and share large samples of clinical trials data across research groups, because everyone collects the data according to their own preferences and definitions. This limits researchers' ability to use a patients' clinical data and to match it to data from new techniques, like genomic testing, to make discoveries. The Pediatric Cancer Data Commons (PCDC) designs better ways to collect and store these clinical data and to connect these data to other types of data, such as imaging data (x-rays, CT scans) and genomic data, by developing and documenting a common language and standards. This allows others to see how our researchers are collecting, storing, sharing, and using clinical trials data so that others can also conduct research in the same way and then easily share and compare data sets across the world. The PCDC Consortium members are dedicated to gathering as much data as possible from around the world into a "data commons" - a single place where researchers everywhere can go to access these data so that they can explore the data and select the subsets of data that are useful for answering their research questions. Fund administered by The University of Chicago.

Cancer cells grow and divide faster than normal cells and therefore have an increased demand for building blocks compared to normal cells. The metabolic pathways that supply these building blocks are often altered in tumors to meet the increased demand. Because cancer cells rely on these metabolic pathways they can be targeted by chemotherapeutics to block cancer growth. Dr. Sabatini and colleagues recently identified a new group of genes that play an important role in one metabolic pathway that supplies cells with the necessary building blocks. He is testing whether these genes can be used as new drug targets to treat cancer and identify additional genes in the same metabolic pathway that might also serve as drug targets. This work will help the development of new chemotherapeutics with less toxic side effects.