Grants Search Results

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.

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.

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.

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.

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.

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.

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) 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.

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

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

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

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

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

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

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

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

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

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

This grant is funded by and named for Jack's Pack - We Still Have His Back, a St. Baldrick's Hero Fund. Jack Klein was a ten year old who loved life, laughing and monkeys. During his illness, his community of family and friends near and far rallied around him under the moniker "Jack's Pack". Their slogan was "We have Jack's Back". After Jack succumbed to Burkitt's Lymphoma, his "pack" focused their energy and efforts to funding a cure...just as Jack would have wanted.

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