Grants Search Results

Survivors of cancer have a higher risk of health problems because of the severity of the chemotherapy and radiation treatments they received. As survivors of childhood cancer age, they increasingly succumb to the "late effects" of their cancer treatment (such as second cancers and heart and lung disease). After 10-15 years, these late effects become the leading causes of death in this population. Adolescents and young adults (AYAs, aged 15-39) are a subgroup of cancer patients that are defined as high risk because they: more commonly suffer from toxicities and side effects of their cancer treatment; have unique barriers to accessing health care; and suffer specific psychosocial concerns because of their life stage transitioning into adulthood. To date, little research has been done on the factors that influence long-term health outcomes in the population of survivors of AYA cancer. Dr. Moke is working to explore how cancer and its treatments affect health later on in life in survivors of AYA cancer, identify the causes of death in this population, and determine what factors and cancer treatments are associated with these specific life threatening health problems. This study will provide the baseline data needed to design ways to decrease the severity of and death from these late effects, and thus be an important step in promoting long and healthy lives in survivors of AYA cancer.

Ewing sarcoma is an aggressive bone and soft tissue cancer that primarily affects children and adolescents. Patients often suffer severe side-effects from treatment and there are no second-line therapies for relapsed tumors. It is critical that we develop new and less toxic treatments for this cancer. Ewing Sarcoma is caused by a rearrangement of DNA that fuses pieces of two different proteins together to form a new protein. This new protein, called EWS-FLI1, can turn on genes that should not be on, leading to the transformation of the cell into an Ewing Sarcoma tumor. This fusion protein has features that make it very difficult to study, it sticks to itself and does not have a structure, a good analogy is that it behaves like a piece of cooked spaghetti. As the Shohet Family Fund for Ewing Sarcoma Research St. Baldrick's Scholar, Dr. Libich is utilizing his background in working with similar proteins that do not have structure. He is using NMR (nuclear magnetic resonance) which works just like MRI, to peer into the protein to understand exactly how it functions. This information is critical for designing molecules (drugs) that will be able to only affect the function of EWS-FLI1 and thus open new ways of attacking Ewing's sarcoma. This grant is funded by and named for the Shohet Family Fund for Ewing Sarcoma Research. In his freshman year of college, Noah was diagnosed with Ewing sarcoma. He endured many months of chemotherapy and had limb salvage surgery. Able to return to school, Noah had no evidence of disease for 2½ years until April 2018 when routine scans revealed he had relapsed. He passed away in May 2021 at the age of 25. Noah and his family were always passionate about the need for curative treatments for diseases of the AYA population. The Shohet family intends to raise funds for this Hero Fund in Noah's memory to find cures for Ewing sarcoma and to carry on his legacy of possibilities and hope.

Based on progress to date, Dr. Ou was awarded a new grant in 2022 and 2023 to fund an additional year of this Scholar grant. Due to the tumor and treatment damaging the developing brain, 60-80% of pediatric brain tumor survivors experience long-term neurocognitive impairment. There are two possible paths to improve outcomes: intervene the adverse brain development after treatment, or further optimize radiotherapy dose distribution in the brain before treatment. For the former, the question is to find at-risk patients to intervene after treatment. For the latter, the question is to find target brain regions, where changing radiation doses can potentially change outcomes. Both questions have been studied on the population-level, not on the individual level. This project aims to push our knowledge in these two fronts to the individual level. Dr. Ou is using data from 3 just finished clinical trials to find target patients and find target brain regions for radiation dose optimization. Compared to studies that consider one risk factor a time, Dr. Ou will consider a comprehensive set of risk factors to improve precision to the individual level. The results will allow him to design future larger-scale, multi-site retrospective replicative and eventually prospective clinical trials, to improve neurocognitive outcomes in this vulnerable population before and after treatment. This grant is generously supported by the Grace for Good Fund, established in honor of Grace Carey and celebrates her survivorship from medulloblastoma. Her cancer journey began in 2007 when she was diagnosed at age 5 with a treatment regime that entailed surgery, proton beam therapy and chemotherapy. While Grace handled it all with minor setbacks, she now faces the physical, emotional and cognitive challenges wrought by the very medications and procedures that saved her life. This fund was inspired by Grace’s desire to help other kids with cancer and supports research of brain tumors and the multitude of challenges facing survivors post treatment.

Pediatric acute leukemias are aggressive blood cancers that result in many childhood cancer deaths despite intensive treatments. Because these leukemias are highly sensitive to radiation, researchers have developed a technology called radioimmunotherapy. Radioimmunotherapy uses antibodies to deliver a radiation payload directly to cancer cells. Most existing radioimmunotherapies are directed against two cell surface proteins called CD33 or CD45. However, because these proteins are also found on many normal blood cells, the amount of radioimmunotherapy that can be safely given via CD33 or CD45 antibodies is limited. As the recipient of the Emily Beazley's Kures for Kids Fund St. Baldrick's Research Grant, Dr. Walter is developing and rigorously testing a new form of radioimmunotherapy that is directed against CD123. CD123 is found on only a few normal blood cells but is heavily expressed on leukemia cells in most children with acute leukemia. Moreover, CD123 is particularly attractive as a target as it is widely overexpressed on underlying leukemic stem cells (the rare cells that have the ability to generate and fuel these cancers), whereas normal blood stem cells express little or no CD123. These studies are the first to test the value of CD123-targeting radioimmunotherapy and will guide researchers towards bringing this new, less toxic treatment to pediatric patients. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma. Her cancer was extremely aggressive, and she bravely battled it through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle. She inspired a community to come together to show love and changed lives with her message: “You gotta stay strong, you gotta stay positive, no matter what happens.” Emily passed away in 2015 at age of 12. She often talked about her dream of starting a foundation that funded research. She named it “Kures for Kids”. Her family and friends carry on her dream and her mission with this Hero Fund.

Dr. French is studying one of the most deadly childhood and adolescent cancers known, called NUT midline carcinoma. There is no effective treatment for this cancer, which has a median survival of 6.7 months. Recently, his team discovered a new class of drug, called 'NEO', that in preliminary studies appears promising in models, an unprecedented finding that gives some hope that they may have stumbled across a new effective treatment for this disease. Based on some recent studies, Dr. French thinks that the drug class directly acts against the cancer protein that drives NUT midline carcinoma, called BRD4-NUT. BRD4-NUT is created by a mutation that fuses one gene, BRD4, to another, NUT, which alone don't cause cancer, but when fused together create a very potent cancer protein. He think the drug inhibits both the BRD4 and NUT halves of this fusion in a manner that gives the drug some selectivity for BRD4-NUT. The findings are exciting because the NEO drugs are set for clinical trials to begin in 2019. Dr. French and colleagues are working to 1) validate the findings that the NEO drugs work well in models bearing NUT midline carcinoma to provide rationale to enroll NUT midline carcinoma patients onto these trials, and 2) determine scientifically how the NEO drugs inhibit NUT midline carcinoma growth.

Altering chemotherapy, including dose intensification, has not improved the survival for osteosarcoma (OS) patients. Genomic analysis has been unsuccessful in identifying consistent targetable options, and there were no responses in relapsed/refractory OS patients treated in numerous Phase I or II trials. Identifying new therapies is imperative. Immunotherapies such as dendritic cell vaccines (DCV) and checkpoint inhibitors have shown activity against adult cancers but there are no studies in children or adolescents (AYA) with OS. Dr. Kleinerman and colleagues demonstrated the efficacy of checkpoint inhibitor therapy against OS lung metastases. They have also showed that the activity of DCV can be improved by checkpoint inhibition. They are investigating whether a unique dendritic cell vaccine that augments T-cells is effective against primary and metastatic OS. This project aims to identify new therapeutic approaches for treating children and AYAs with relapsed/metastatic and primary OS. If efficacy is demonstrated, this approach can be translated into a clinical trial for children with OS lung metastases. Another goal is to combine vaccine therapy with chemotherapy for newly diagnosed patients to improve disease-free survival.

Thanks to advanced diagnosis and treatment, many children now can be treated from cancer and stay alive for a long time; they are called survivors. Some anticancer drugs are harmful to the heart and may cause heart failure in these survivors. High blood pressure increases the risk of heart failure in survivors, but no one knows how this happens. Dr. Zordoky has developed a new model to answer this question. He thinks that anticancer drugs make the hearts age faster leading to a worse response to increased blood pressure. He is looking at a natural compound and a new group of drugs which prevent aging to see if they will protect the hearts from the bad effects of anticancer drugs and make the hearts stronger when hit by high blood pressure. The findings of this research will open the door for testing these compounds in the clinic in order to prevent late side effects of anticancer drugs in survivors.

Cancer associated with different types of lymphocytes is known as lymphoma. Different forms of lymphoma are a common cause of pediatric cancer in the US. Current clinical therapy is based on conventional chemo- and radiation therapy, which is associated with numerous side effects. As the recipient of the Jack's Pack - We Still Have His Back St. Baldrick's Research Grant, Dr. Bahal is researching an alternative robust therapy against lymphoma by exploring new chemically modified therapeutic molecules and their interaction with novel targets. One of the major challenges associated with current therapies are side effects due to non-targeted delivery of the drug to the normal bystander cells that can result in potential toxicity. Dr. Bahal is using a nanotechnology based approach for targeted delivery. He aims to accomplish two specific goals: a) To optimize the design and synthesis of a new class of bioactive molecules to target pediatric lymphoma; and b) To test the therapeutic effect of synthesized molecules in disease-related models. Investigation of these novel methods will lead to the development of novel drug candidate for pediatric lymphoma. Jack Klein was a 10 year old who loved life, laughing and monkeys. During his illness, his community of family and friends near and far rallied around him under the moniker "Jack's Pack". Their slogan was "We have Jack's Back". After Jack succumbed to Burkitt's Lymphoma, his "pack" focused their energy and efforts to funding a cure...just as Jack would have wanted.

Adolescent and young adult (AYA) cancer patients face depression and anxiety that are unique to their cancer diagnoses. Existing psychotherapies that work well for general depression and anxiety do not work effectively for the AYA population. Untreated psychological stress and distress (like depression or anxiety) will result in young patients' non-compliance to medical treatment, low quality of life among others. These psychological challenges stand in the way between these patients and a successful recovery. Therefore, as the recipient of the Julia's Legacy of Hope St. Baldrick’s Supportive Care Research Grant, Dr. Zhang is developing and evaluating a computer-based cognitive behavioral therapy that is specifically tailored for AYA cancer patients. Results of this study will improve the treatment for AYA cancer patients' depression and anxiety to improve their medical compliance and quality of life. This grant is funded by and named for Julia's Legacy of Hope, a Hero Fund that honors her positive, courageous spirit and carries out her last wish: "no child should have to go through what I have experienced". Diagnosed at 16 with Ewing sarcoma, Julia fought cancer and survived only to be stricken by a secondary cancer as a result of treatment. Her family hopes to raise awareness and funds for research especially for Adolescent and Young Adult (AYA) patients.

This grant funds a graduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. HPV vaccination is an important but underutilized tool to ensure the long-term health of childhood and adolescent cancer survivors. Survivors of childhood and adolescent cancers are at higher risk for HPV-related health risks, including HPV-related cancers, than the general population. Unfortunately, their rate of HPV vaccination is much lower than the general population. This study will explore communication strategies related to the HPV vaccine among survivors being seen for follow-up care in an oncology setting. Interviews will be conducted with survivors (ages 18-26) as well as parents of survivors to understand their concerns about and barriers to HPV vaccination and to create specific communication strategies for oncology providers to discuss the HPV vaccine with survivors.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. More than 80% of children with cancer before the age of 20 years will survive beyond 5 years from diagnosis. The exposure to chemotherapy causes both short-term as well as long-term health issues in these individuals. Exercise interventions in adults with cancer demonstrate significant benefits in health, however, there are no studies examining the effects in pediatric, adolescent and young adult cancer survivors. This study will determine if a one-on-one supervised exercise program or exercise intervention personalized for adolescent and young adult (AYA) cancer survivors (15 and 29 years age) will significantly improve chemotherapy-induced health issues.

The shape and function of bone, fat, muscle, and other connective tissues evolve through a carefully orchestrated process that leads mesenchymal stem cells (MSCs) to progressively differentiate into more lineage-restricted tissue-specific phenotypes. As this occurs, MSCs must interpret their surrounding extracellular milieu. When everything works correctly, normal mesenchymal tissues emerge. When disrupted, as tragically occurs with Ewing sarcoma (ES), the aberrant fusion protein (FP) acts as powerful transcription-factor that corrupts the epigenetic program and locks ES in an undifferentiated state unable to interpret or respond to the biophysical cues present in the tumor microenvironment. Attempts to understand the FP’s effect upon tumor-ECM interactions within monolayer culture systems that lack a native tumor microenvironment has contributed, not unexpectedly, to spurious results that overestimate the clinical effectiveness of chemotherapy. To close this gap, Dr. Ludwig's multi-disciplinary team is using an innovative 3D tissue engineered model, pioneered by his laboratory, to assess next-generation EWS-FLI1-targeted therapies within a physiological microenvironment that cannot readily be studied in vivo. This project will shed new light on ES biology and promises to improve the ability to co-target the FP and other proteins that maintain the aggressive, poorly differentiated state of ES. This grant is generously supported by 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. This Hero Fund honors his courageous fight and hopes to raise funds for Ewing sarcoma research.

We can now manipulate the immune system with remarkable precision and efficacy to fight certain cancers. However, tumors adapt to reduce immunotherapy efficacy. This is true for solid tumors including osteosarcoma. Therapy-refractory metastatic osteosarcoma represents a pressing unmet need, as the outcome has not improved for over 3 decades. This multi-institutional collaborative proposal explores tumor-extrinsic pathways by which pulmonary metastatic osteosarcoma evade immunity. Dr. Huang’s team is focusing on key molecules responsible for such evasion, against which existing or emerging therapeutic agents are available currently or in the very near future. Therefore, uncovering these pathways could realistically offer multiple new clinical trials for pediatric and AYA metastatic osteosarcoma in the next 3 years. This Osteosarcoma Collaborative St. Baldrick's Grant to Cure Osteosarcoma is funded through the generosity of the Osteosarcoma Collaborative.

Despite the use of multimodal treatments and the implementation of several clinical trials worldwide, pediatric cancers survival rate has come to a standstill for the last decade. Moreover, intensive therapies are not devoid of long-term side effects, notably increasing lifetime risk for secondary malignancies. The duty of the pediatric oncologist is to propose the most adequate treatment to cure pediatric patients with the best quality of life for a long time. Therefore, understanding the biological underpinnings of pediatric malignancies is crucial to develop new therapeutic paths adapted to the specificities of a young organism. A major pitfall is the lack of adequate experimental models. To overcome this problem, Dr. Broutier is developing patient-derived 3D-organoid models (mini-tumor growing in a dish) of pediatric cancers. Beside their broad interest for research community, she will use them to identify mechanisms involved in cell death resistance in pediatric cancers, as a key step towards development of new targeted therapies adapted to children and adolescents.

Adoptive immunotherapy has demonstrated unprecedented clinical success in the treatment of leukemia. 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. This protein increases "specificity," the ability to recognize cancer cells, and "function," the ability to destroy those cancer cells. An important challenge in cellular immunotherapy is to minimize the manipulation of patients' T cells outside the body. Prolonged culture protocols trigger functional exhaustion and compromises their efficacy upon return to the body. A critical issue involves the pre-requisite "activation" step necessary for CAR expression on the cell surface of T cells. By optimizing culture conditions, Dr. Ghassemi developed approaches to express CAR in dormant T cells without the need for activation. Importantly, her preliminary findings show that elimination of this activation step retains effector function and potency of CAR T cells in models of the pediatric cancer ALL. This project is providing insight into the regulatory components influencing CAR expression in dormant T cells which will lead to superior CAR T cells for cellular immunotherapies against ALL. This grant is supported by TEAM ABBY Gives, a St. Baldrick's Hero Fund. Abby was diagnosed with Pre-B ALL when she was almost five years old. She had a successful bone marrow transplant, but battle battled graft vs. host disease (GVHD) for years. Abby and her treatment team worked hard over many years to keep the GVHD in check. Sadly, Abby passed away on October 19, 2021. This fund unites the incredible support of family and friends in Abby's memory and inspires others to join the fight for cures and better treatments.

Osteosarcoma is the most common primary bone tumor in childhood. The survival rate remains dismal, mainly due to ineffective therapeutic approaches for the relapsed/metastatic patients. One major obstacle of treating osteosarcoma is lack of suitable preclinical models. Dr. He's studies have established the first cultured osteosarcoma tissue model (an organoid). Dr. He aims to establish the first biobank of osteosarcoma organoids from patients as an open resource for the field, and utilize this organoid biobank to evaluate a novel class of therapeutics targeting key signaling pathways in osteosarcoma cells. This study will provide a powerful platform for predicting clinical treatment responses and developing new therapeutics for treating osteosarcoma.

Despite recent advances in technology, very little is known about many types of rare and high risk childhood cancers. Since the numbers of these patients are so small, it has been very difficult to study how best to take care of them. Dr. Potter is using technology to look at the genetic code of these rare tumors, in order to learn more about why and how they occur, as well as how they change over time. This knowledge will help to create tests to diagnose these patients, as well as to develop more effective, less toxic treatments. This grant is generously co-supported by the Invictus Fund and O Danny Boy I Love You So: The Danny O'Brien Rhabdoid Tumor Research Fund. The Invictus Fund was created to honor the memory of Holden Gilkinson who was diagnosed with Stage IV anaplastic Wilms tumor when he was 3 years old. Holden endured intense treatment and surgery, eventually losing both kidneys. He passed away just a few days shy of his 7th birthday. Through it all, Holden’s unconquerable spirit and love for life prevailed and is personified in the poem “Invictus” by William Ernest Henley. Danny O’Brien was just 5 months old when he was diagnosed with a malignant rhabdoid tumor on his liver. This cancer is extremely rare and aggressive. He endured chemotherapy to shrink the tumor for surgery, but the treatment was not effective. At the tender age of 9 months, Danny passed away. Fortunately, he knew nothing but love and affection all of his short life. This fund honors Danny’s courage and his unconditional love even in the midst of his battle with cancer.

Cancer cells rely on specific nutrients for growth and survival, rendering nutrient restriction as a potential therapeutic strategy. Along this line, acute lymphoblastic leukemia (ALL) cells have been found to be dependent on exogenous supply of asparagine, a nonessential amino acid, for protein synthesis. As a result, depletion of asparagine in the blood stream by L-asparaginase, a chemo-agent, has been successfully used to treat pediatric ALL for 40 years. However, ALL patients can develop resistance to the continuous application of this chemo-agent. Dr. Zhang is determining how ALL cells become resistant to L-asparaginase treatment, and therefore to provide experimental evidence of novel therapeutic targets that can potentially improve the outcome in pediatric ALL patients.

Sarcomas are tumors of the bone and soft tissues that comprise up to 20% of cancer diagnoses in children. Despite dismal outcomes for patients with recurrent or metastatic disease, treatment regimens have remained largely unchanged for decades – intense non-specific chemotherapy combined with surgery or radiation. Dr. Tulpule studies Ewing’s sarcoma (ES), a bone tumor caused by a unique genetic change that creates a tumor-specific protein EWS-FLI1. To date, no drug has been identified to directly block the cancer causing EWS-FLI1 protein. His research takes a different approach to combating ES by asking a fundamental question: can we identify a targetable weakness in ES tumors that is caused by the EWS-FLI1 protein? Using a cutting-edge screening technology called CRISPR interference, Dr. Tulpule's team identified a specific vulnerability in ES cells’ capacity to repair damage to their DNA. Normal cells have many backup systems in place to repair DNA damage, but they have shown that EWS-FLI1 causes ES cells to become overly reliant on a single pathway, known as homologous recombination (HR) repair, such that blocking HR is an effective and specific way to kill ES. Dr. Tulpule is building a detailed understanding of why ES cells are so vulnerable to HR pathway blockade and then applying that knowledge towards developing less toxic and more effective treatments for ES patients.

Phthalates are chemicals added to many products that we use every day, including some common medications. Phthalates interfere with hormone systems in our bodies, which might cause cancer. Dr. Ahern wants to know if phthalate exposure while in the womb or during childhood increases the risk of childhood cancer. It would usually be time-consuming and expensive to answer this question scientifically. However, Dr. Ahern's team has developed a way to measure phthalate exposure using electronic pharmacy records that is both fast and inexpensive. This technique works because phthalate exposure from medications dwarfs exposure from other products. He will use this technique on existing pharmacy and cancer data from the entire population of Denmark. Dr. Ahern will measure phthalate exposure in pregnant women and in their children, and calculate whether that exposure increases a child's chances of developing cancer. If he finds that it does, we could prevent childhood cancer cases by limiting the amount of phthalates used in consumer products.