Grants Search Results

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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

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

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

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

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

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