Grants Search Results

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.

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.

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.

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.

Acute Myeloid Leukemia (AML) is a heterogeneous disease characterized by malignant clonal expansion of undifferentiated progenitor cells. The relapse and refractory AML is one of the biggest challenge faced by clinicians as significant proportion of patients within this category have very poor outcome. Persistence of leukemic stem cells has been associated with higher risk of relapse, additionally these leukemic stem cells also show drug resistance characteristics. Dr. Lamba’s team has recently developed a gene-expression based pediatric leukemic stemness score and drug resistance score that has shown promising results in not only identifying patients with higher risk of relapse and poor outcome but is also suggestive of response post-transplant. Dr. Lamba is also focused on inherited genetic polymorphisms to study pharmacogenomics markers specific to the standard chemotherapy regimen. We recently developed a pharmacogenomic score for are-C the mainstay of AML chemotherapy that associated with treatment outcome and survival. This project seeks to validate the gene expression and genotype-based scores in large cohort of patients treated on a Children’s Oncology Group clinical trial. The results will prepare a sound scientific rationale to incorporate a preemptive testing of patients for genomics based prognostic score that can be incorporated into the risk stratification of patients to guide precision medicine in AML. 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.

Acute myeloid leukemia (AML) as an aggressive pediatric cancer associated with poor outcomes and few changes in therapies over the past 30 years. The presence of small numbers of persisting leukemia cells after chemotherapy has become an important predictor of leukemia relapse, however, current assays used to detect residual leukemia have limited sensitivity and many patients with “no detectable leukemia” still go on to relapse. This underscores the need to identify and develop novel assays that more accurately determine optimal therapies and that improve upon current leukemia detection approaches for AML. Dr. Meshinchi and colleagues have performed functional genomic profiling (RNA sequencing) in 2000 children, adolescents, and young adults diagnosed with AML over the past 25 years that includes diagnosis, remission, and relapse timepoints. This preliminary data suggests that deep and functional cancer profiling across an unprecedented number of patient samples and timepoints informs relapse risk, enables a precision medicine approach that considers specific alterations within a patient’s specific cancer, and links diagnosis and relapse profiles with the goal of better understanding how/why relapses occur and how best to prevent them. Therefore, Dr. Meshinchi and colleagues plan to leverage this unprecedented dataset to develop an integrated genomic platform that will significantly improve prognostic determination and treatment decisions for children, adolescents, and young adults diagnosed with AML. Successful validation of our assays will therefore fill a critical unmet need in the field of AML, and the resulting product will be an optimized test ready for clinical use.

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.

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.

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.

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.

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.