Grants Search Results

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

Leukemias are the most common cancer of childhood, and most often arise from cells of the B lymphocyte lineage (B cell precursor ALL, or B-ALL). While the prognosis for patients with standard-risk disease is good, the treatment of patients with relapsed or refractory B-ALL is difficult and thus new therapies are needed. Dr. Schuettpelz is studying the role of a cell-surface protein called CD53 in the regulation of malignant B cells. CD53 is more highly expressed on leukemia cells than on normal B cells, and has previously been shown to promote the survival of malignant cells. Using a model of B-ALL as well as human leukemia cells, she will test the effects of CD53 loss and gain on disease development and cell survival. Ultimately, she hopes that CD53 may be targeted therapeutically to treat patients with B-ALL.

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.

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.

Unlike many other pediatric cancers, osteosarcoma has many abnormalities found on genetic analysis of the tumor itself. Dr. Sweet Cordero and colleagues hypothesize that some of these abnormalities could be used to predict what treatment might work best for each specific osteosarcoma patient. For example, many osteosarcomas have genetic alterations that block their ability to "repair" their DNA using specific pathways. One of these defective pathways is called the "homologous repair" pathway and another is called the "alternative lengthening of chromosomes" pathway. The inability of osteosarcoma tumors to repair their DNA using these pathways may make them susceptible to specific drugs. However, it is very likely that these drugs will need to be used in combination and not alone. A key need to advance osteosarcoma patient care is to define and use appropriate model systems to test drugs before using them in patients. This project is combining both preclinical studies in PDX models and a clinical trial to develop new ways to treat osteosarcoma patients with the goal being to improve survival for patients with relapsed and metastatic disease. This multi-year grant is named for and funded by the Battle Osteosarcoma Hero Fund inspired by and established in honor of Charlotte, Dylan, Tyler and all OsteoWarriors. Led by parents, its mission is to raise funds for promising osteosarcoma precision oncology research to improve treatment options and outcomes for kids battling osteosarcoma.