Grants Search Results

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors of infancy. Standard therapies lead to severe toxicities and poor overall survival. Dr. Raabe aims to identify novel therapies to reduce toxicities and improve survival. Dr. Raabe and colleagues found that cancer cells rely on activation of the integrative stress response (ISR) to maintain cell equilibrium and survival. However, if the ISR is activated too intensely or for too long, cells undergo apoptosis and die. Paxalisib and gemcitabine are medications that induce considerable cell stress, further activating the integrative stress response, and extending survival in models of AT/RT. Dr. Raabe is investigating how these medications act together to target cell stress pathways and their impact on survival in models of AT/RT. The findings will translate directly through the International Pacific Pediatric Neuro-Oncology Consortium (PNOC) into a new clinical trial treating children with relapsed or refractory AT/RT. 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.”

Burkitt lymphoma (BL) is the fastest growing, most aggressive pediatric tumor. In the 1960s, it was universally fatal. Over the past decades, clinical trials identified very high dose chemotherapy therapies as effective. Over 95% of children with BL in the US now survive. However, over 80% of cases of BL arise in children in sub-Saharan Africa (SSA) and other lower income regions where high dose chemotherapy is not currently feasible and in these settings BL is typically fatal. In the study, Dr. Allen builds on the observation that BL tumors from US and SSA are largely indistinguishable, but surprisingly tonsils from children in SSA and US have vastly different gene expression patterns. He therefore hypothesizes that the much higher rate of BL in SSA may not be due to intrinsic cancer cell factors, rather due to the nature of lymphoid tissues out of which the cancer cells grow. If Dr. Allen and colleagues can identify factors that lead to BL, they hope to create opportunities to prevent and treat BL in SSA. This grant is funded by Danilo Gallinari and the National Basketball Players Association.

This proposal introduces four groundbreaking advancements in the treatment of Ewing sarcoma (EwS), a rare and aggressive cancer. Firstly, Dr. Li and colleagues aim to optimize and assess the effectiveness of cutting-edge anti-IL1RAP ADCs in treating EwS. Secondly, they seek to uncover new insights into the diversity and heterogeneity of targets within EwS tumors. Thirdly, will explore the potential of innovative bispecific ADCs to target a wider range of EwS cells, enhancing treatment efficacy and reducing the risk of relapse and spread. Lastly, Dr. Li will explore the possibility of applying these advancements to other IL1RAP+CD276+ cancers like acute myeloid leukemia (AML). Overall, this research holds promise for improving outcomes and broadening treatment options for patients with these challenging cancers. This grant is funded by and named for the D-Feet Cancer - The Dalton Fox Foundation. D-Feet Cancer - The Dalton Fox Foundation was established to honor and remember Dalton’s contagious smile and sense of humor, even on his toughest days with Ewing Sarcoma. He is an inspiration and the reason for the mission and interest in finding targeted therapies and treatments for Ewing Sarcoma, a pediatric bone cancer.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk type of B-ALL. Children and adolescents/young adults with Ph-like ALL have greater than 60% relapse risk and experience significant mortality with best-available chemotherapy. Emerging data suggest that patients with Ph-like ALL are more likely to develop immunotherapeutic resistance to treatments. Dr. Tasian, and Dr. Terry Fry at the University of Colorado, and their colleagues are testing whether a new CAR T cell immunotherapy that they developed will decrease the risk of relapse for patients with Ph-like ALL. This work will be the groundwork to translate findings into a phase 1 clinical trial. This grant is supported by The Ty Louis Campbell (TLC) Foundation. TLC was created in memory of Ty, who lost his 2-year battle with brain cancer just days after his fifth birthday. TLC funds innovative research and clinical trials specifically geared toward the treatment of the deadliest childhood cancers (including brain and spinal cord tumors). TLC seeks less toxic, more effective treatments that are specifically designed for children fighting cancer. Their ultimate mission is to help fund the intelligence and technology that will uncover new ways to cure children with cancer.

Adoptive immunotherapy has demonstrated unprecedented success in the treatment of pediatric leukemia. Extending its therapeutic potential to other pediatric malignancies such as glioblastoma (GBM) has proved challenging. In this therapy, T cells are isolated from a patient, expanded outside of the body, and genetically modified prior to reinfusion. The ability of these T cells to recognize and eliminate cancer cells is improved by expressing a protein (CAR) on the T cell surface. An important challenge is to minimize the manipulation of patients' T cells outside the body. Prolonged culture compromises their efficacy. Dr. Ghassemi developed approaches to generate CAR T cells in 1 day. These cells have increased potency. She is combining this recent development with a metabolic strategy to overcome the metabolic nature of tumor environment. This synthetic advancement combined with the production of CAR T cells in 1 day will lead to superior CAR T cells for cellular immunotherapies against pediatric GBM. This grant is funded by and named for the Be Brooks Brave Fund. Despite his diagnosis at age 5 with inoperable brain and spinal tumors, Brooks taught so many people what life is truly about--love. He was BRAVE beyond his years with an inspiring “faith over fear” attitude. This Hero Fund hopes to raise money for high-grade glioma research so no other family will hear the words, “there is no cure”.

There has been little recent progress in treating Ewing sarcoma, a pediatric tumor involving bone. Dr. Stegmaier and colleagues have used a technology called CRISPR to identify urgently needed, new therapeutic targets for this disease. They prioritized a class of targets which are expressed in immature but not mature tissues. These proteins are often abnormally re-expressed in cancers such as Ewing sarcoma. Thus, drugs targeting these proteins would be expected to have minimal toxicity. The Stegmaier lab identified the target IGF2BP1 as a top selective gene dependency in Ewing sarcoma; deletion of IGF2BP1 was more deleterious to Ewing sarcoma than all other cancer types screened. Importantly, IGF2BP1 is not expressed in most normal human cells. Dr. Stegmaier will validate IGF2BP1 as a therapeutic target in Ewing and will determine the mechanisms by which Ewing sarcoma cells rely on IGF2BP1 for growth. With IGF2BP1 chemical inhibitors in development, this project has exciting translational potential for patients with Ewing sarcoma. This grant is funded by and named for The Ben Brandenburg Fund for Ewing Sarcoma Research. Ben passed away at the age of 15. He is remembered for his quick wit, indomitable spirit and bravery. This fund is his lasting legacy and ensures that research is funded so fewer children will have to suffer from Ewing Sarcoma.

The majority of children with newly diagnosed Burkitt lymphoma (BL) are cured. Unfortunately, the outcome is poor for patients whose disease returns (relapse). The relapse is caused by multiple reasons but mainly is due to drug resistance and suppression by the tumor surroundings. Novel therapeutic approaches are urgently needed. Natural killer (NK) cells can attack cancer cells. Dr. Cairo is developing immunotherapeutic agents to enhance the functions of NK cells to kill BL. Expanded NK cells will be modified by genetic techniques to specifically target CD20 and a special protein will be developed to bind to another surface protein CD19 on BL. A virus will be created to secrete IL21 to enhance NK persistence and function. If successful, the combinatorial therapies will become available to pediatric BL patients in the clinical setting and would offer a potentially more effective and less toxic therapeutic approach, ultimately leading to improved survival. 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.

Ewing sarcoma, an aggressive bone cancer that occurs in children and young adults, is caused by an abnormal chimeric protein (EWS-FLI1) that prevents cells from maturing into normal connective tissues through a process known as cell differentiation. How EWS-FLI1 acts to stop differentiation, however, remains an enigma. To solve this problem, Dr. Ludwig uses powerful gene editing tools to systematically turn the EWS-FLI1 protein up or down, then measures whether such changes allow cancer cells to behave more normally. The information gained from this research is expected to lead to new anti-cancer treatments for adolescents and young adults battling Ewing sarcoma. This grant is named for The Shohet Family Fund for Ewing Sarcoma Research. Noah was diagnosed with Ewing sarcoma in his freshman year in college. After limb salvage surgery and chemotherapy, he was able to return to school. Two years later, Noah relapsed and sadly passed away. This Hero Fund honors his courageous fight and hopes to raise funds for Ewing sarcoma research.

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 2022 SBF-AACR Award for Outstanding Achievement in Pediatric Cancer Research went to Dr. David Malkin at The Hospital for Sick Children (SickKids). Dr. Alanna Church at Boston Children's Hospital received the 2022 research grant. Dr. Church's research interests are in bringing molecular testing to the clinical care of children with cancer to improve diagnoses and treatments.

Childhood Hodgkin lymphoma (a cancer of white blood cells) is highly curable. Modern chemotherapy regimens effect a cure in over 95% of children diagnosed, however, about 15-20% will suffer a recurrence of their lymphoma and need additional highly intensive chemotherapy and bone marrow transplantation. These intensive regimens have many serious chemotherapy-related side effects (infections, mouth sores, etc.). Dr. Wadhwa’s study will investigate a novel predictor of cancer relapse and serious chemotherapy-related side effects by studying the role of body composition at Hodgkin lymphoma diagnosis in cancer-free survival and chemotherapy toxicities. Body composition has already been shown to be a significant predictor of cancer relapse and chemotherapy toxicities in adults with cancer. Dr. Wadhwa’s team will examine the body composition of children at cancer diagnosis, its association with cancer-free survival and serious chemotherapy related toxicities, how body composition changes during cancer treatment, and whether changes in body composition during cancer treatment impacts survival. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

Diffuse midline glioma (DMG) is an aggressive pediatric cancer and outcomes are dismal, with a life expectancy of less than a year. It is particularly difficult to treat as they are commonly located in the brainstem near sensitive structures, meaning that surgical removal is not feasible. Recent advances in technology have led to development of “liquid biopsy,” which works by detecting small pieces of DNA that break off from the tumor and are found in the cerebrospinal fluid (CSF) and blood (termed cell-free DNA, cfDNA). This is important because these “liquids” are typically much easier to access than the tumor itself, which is particularly important in these brainstem tumors. Dr. Souweidane’s project will monitor cfDNA in the cerebrospinal fluid (CSF) and blood of DMG patients over time. In this study, Dr. Souweidane will implant ventricular access devices at time of standard biopsy in newly diagnosed DMG patients to provide on-going minimally-invasive access to CSF, and then will integrate this assay into early-stage clinical trials for DMG patients to see if it can be an effective biomarker of early response. Dr. Souweidane’s team believes the completion of these experiments will establish the utility of cfDNA liquid biopsy in DMG and will also, by guiding decision-making and management for brain tumor patients, dramatically change how we treat these devastating diseases. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

This project focuses on engineering a component called a macrophage. Macrophages talk to T-cells, using a protein called a cytokine, helping to boost T-cell effects and eradicate a child's cancer. Macrophages within children who respond to engineered T-cells long term (do not relapse) are able to release cytokines or talk with T-cells more effectively. On the reverse side of that same coin, those small percentages of patients who present with serious side effects have macrophages that are too effective at talking to T-cells or are releasing too many cytokines. Dr. Gustafson is developing a new technology that predicts how effective macrophages will be at talking to T-cells. This technology can be used to prevent toxicity and reduce relapse, allowing for more kids to live healthy cancer-free lives. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

More children die from brain tumors than any other type of cancer. Pediatric high-grade gliomas are the type of childhood brain tumor that is the hardest to treat and the most likely to result in death. Researchers have learned that pediatric high-grade glioma is actually several different types of tumors that are driven to grow by different genetic changes in the tumor cells. Almost all clinical trials have shown that chemotherapy doesn’t cure more kids and just leads to more side effects, however a clinical trial completed almost 10 years ago, used two chemotherapy medicines, in addition to surgery and radiation, and cured significantly more patients than previous therapy combinations. Dr. Green will use modern pathology tests to figure out the pediatric high-grade glioma subtype for all of the patients from that previous trial. Dr. Green and colleagues will look at the survival on each trial by subgroup to know which subgroup(s) showed better survival with the addition of one of the chemotherapy medicines to their treatment. Answering this crucial question will change the future of pediatric high-grade glioma treatment. With these results, current pediatric high-grade glioma patients will be able to be given the right standard treatment to maximize their chance of survival and minimize side effects. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

Although Hodgkin Lymphoma (HL) is largely curable, 10-20% of patients are resistant to treatment and difficult to cure. When a patient’s cancer comes back or does not respond to chemotherapy, it is often because the immune cells have become exhausted and unable to recognize the cancer cells in the body. The first goal of Dr. Bollard’s project is to determine if newer immunotherapy drugs called PD1 inhibitors, when given in combination with the administration of a novel cancer killing T-cell therapy, will produce long-lasting cures in patients with high-risk lymphoma with less side effects than conventional chemotherapy. Dr. Bollard and colleagues will take a patient’s immune cells and re-educate them in the laboratory to recognize antigens on the cancer cells and then give the T cells back to the patients to redirect them to the cancer cell. The second goal of this project is to genetically modify the cancer killing T cells and express a chimeric antigen receptor (CAR), which will enable the T cells to recognize a protein found in HL and to destroy the cancer cells more effectively. Dr. Bollard’s team proposes a novel approach of combining CAR technology with a tumor antigen specific T cells into a single “living drug” that will produce a robust response and provide a long-lasting immunity using the patient’s own immune system. This therapy has the potential to benefit not only children with HL, but other solid cancers such as neuroblastoma and brain tumors, where the environment surrounding the cancer cells make it difficult for T cells to infiltrate and kill. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

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 2021 SBF-AACR Award for Outstanding Achievement in Pediatric Cancer Research went to Dr. Crystal Mackall at Stanford University. Dr. Robbie Majzner at Stanford University received the 2021 research grant. Dr. Majzner's research interests are in immunotherapy and solid tumors.

Pineoblastoma (PB) is a rare, highly malignant form of brain tumors in children arising from the pineal gland, a tiny organ deep within the brain. The average 5-year survival rate of PB patients is 58%, but drops to 15% in children less than 5 years of age. Because of the location of the tumor, PB can be very difficult to treat. Current treatments include surgical resection followed by radiation and chemotherapy, however, a significant proportion of surviving patients suffer from severe treatment-related late effects and tumor recurrence. Thus, this presents an urgent need for novel therapeutic modalities to improve PB patient survival while minimizing adverse side effects. Proton therapy is one of the most precise and advanced forms of radiation therapy with pencil-beam scanning that allows for specific treatment of tumors, while sparing surrounding healthy tissues. Recently a highly targeted form of proton therapy, known as “FLASH”, with an ultrahigh dose rate, shows less toxicity and improved healthy tissue sparing, while maintaining effectiveness in eradicating tumor cells. As the recipient of the Lauren’s Pediatric Pineoblastoma Fund Research Grant, Dr. Lu and colleagues are investigating the impact of novel FLASH proton treatment strategies on PB growth and recurrence. This research will further define tumor cell diversity and identify treatment-resistant cells and mechanisms in relapsed tumors, as well as determine the effectiveness of combined proton therapy with immunotherapy on PB. These studies will establish proof-of-principle for potential effective therapeutic interventions in PB eventually leading to reduced long-term treatment related side effects and better survival outcomes for patients with this devastating cancer. This grant is funded by and named for Lauren’s Pediatric Pineoblastoma Fund. Lauren was diagnosed with pineoblastoma at the age of 3 and relapsed two years later. She has spent half her life in treatment but is defying the 5% survival odds given at relapse as a disease stable, happy 11 year old today. But her family lives with daily uncertainty because chemotherapy is no longer effective and Lauren has visible tumors in her brain and spine that have been dormant for two years. They are acutely aware there are no treatment options. This Hero Fund was established with the goal of making it possible for researchers to include pineoblastoma in brain tumor treatments.

High-risk neuroblastoma is a very aggressive childhood solid tumor and approximately only half of patients with high-risk neuroblastoma survive. Dr. Goldsmith will be evaluating biomarkers of an antibody drug targeting GD2 and chemo-immunotherapy in three active clinical trials within the Children’s Oncology Group. Performing the same biologic correlative assays across three trials will not only answer key clinical questions regarding GD2 targeted therapy response in patients at different stages of treatment, but also provide an unprecedented opportunity to evaluate novel biomarkers that may guide treatment for future patients. Dr. Goldsmith hypothesizes that rational selection of therapy based on results of validated biomarker studies will improve the care of children with newly diagnosed high-risk neuroblastoma, thereby reducing the number of children who relapse and reducing the burden of acute and late effects of therapy. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

Neuroblastoma (NB) is the most common solid tumor in children outside of the central nervous system and children with high-risk NB typically have poor outcomes despite long and toxic upfront therapy. This project will define the evolution of the CAR natural killer T (NKT) cell program post-infusion using peripheral blood and tumor samples. Dr. Heczey will measure the effect of CAR-NKTs on cancer cells, the tumor-associated macrophages (TAMs), and other tumor components and vice versa at the single-cell level. Additionally, Dr. Heczey’s team plans to characterize the interactions between CAR-NKTs and tumor cells with the aim of determining how CAR-NKTs can overcome the challenges and counterattacks mounted by the NB tumor. The results of this project should identify molecular programs of CAR-NKT cells that are crucial to fighting cancer cells; such findings will be highly informative in boosting the anti-tumor activity of NKT cells for cancer immunotherapy. This study will advance the development of an effective, safe therapy for children with relapsed or refractory high-risk NB and should inform the next generation of cell-based immunotherapies This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

Proteins on the surface of cancer cells provide some of the most promising target for new therapies in children with acute myeloid leukemia (AML). It is important to know actual number of molecules of mesothelin and E-selectin on the surface of the cell and how expression differs from patient to patient. Dr. Kolb will look at leukemia cells from 100 children enrolled on a Children's Oncology Group Phase III trial to quantify the amount of mesothelin and E-selectin on the leukemia cells for each. This data will provide proof that the assay works and can be used to determine eligibility for a clinical trial of mesothelin and E-selectin target therapies. Additionally, Dr. Kolb and colleagues will create a web-based portal for physicians to access the expression data for these other proteins on the surface of the leukemia cells. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.

Despite breakthroughs in cancer biology, pediatric solid tumors have seen minimal improvement in patient outcomes. Neuroblastoma, the most common solid tumor malignancy of childhood, encapsulates the full spectrum of cancer heterogeneity. Dr. Mosse’s team have shown that a specific ALK inhibitor is far superior than the current targeted therapy being tested in a Children’s Oncology Group Phase 3 trial for patients with an ALK genetic alteration. To ensure that the proper clinical and correlative studies are done to identify all patients whose tumors harbor an ALK genetic alteration using a custom-designed and targeted deep sequence capture panel. In parallel, Dr. Mosse and colleagues will adapt this panel to capture circulating tumor DNA (ctDNA) in the blood, also called “liquid biopsies,” of these patients and follow them over time to learn how they respond to our therapies and if/how their tumors develop resistance. While liquid biopsies have become a validated clinical tool in a subset of adult malignancies, its utility in pediatric cancers remains unproven. Liquid biopsies have the potential to overcome many of the limitations we face with solid tumors, as ctDNA abundance tracks with disease burden, reliably captures tumor genomic heterogeneity, and portends patient outcomes. Dr. Mosse and colleagues hypothesize that there is a critical unmet need to harness minimally invasive ctDNA assays to elucidate actionable targets in high-risk neuroblastoma, monitor response to therapy and disease burden, and establish circulating nucleic acid detection as a clinical biomarker for pediatric solid tumors. This grant is funded through a partnership between the St. Baldrick’s Foundation and the American Cancer Society.