Grants Search Results

Despite cure after cancer, the majority of childhood cancer survivors are diagnosed with chronic health problems such as diabetes, hypertension, or heart disease within 30 years of cancer diagnosis and treatment. Hypertension and diabetes are important health problems associated with heart disease and result in early death compared to survivors without heart disease. Compared to siblings, childhood cancer survivors treated with radiation have a higher risk of developing diabetes at a young age. Even though important, the reasons for developing diabetes in cancer survivors are poorly understood. Insulin is an important hormone and affected by cancer treatment. Dr. Mostoufi-Moab is for the first time examining cancer treatment effects (radiation vs. chemotherapy) on making insulin and breaking down blood sugar in childhood cancer survivors, age 15-30 years. She will use tests to measure glucose breakdown, insulin secretion, and mathematical modeling to evaluate the body's handling of fat, all important steps for understanding the why cancer therapy causes diabetes in CCS. Understanding the steps leading to diabetes will help doctors chose the correct treatments for diabetes and for scientists to test options to prevent diabetes in cancer survivors. Achieving these goals will improve quality of life and avoid early death due to cancer treatment-related conditions in childhood cancer survivors.

Many chemotherapy drugs used in childhood cancer have the potential to damage peripheral nerves and thus may impact a child’s ability to function. Early detection of this nerve damage is important to tailor treatment plans and initiate rehabilitation interventions. Currently, no measure of chemotherapy-induced peripheral neuropathy (CIPN) exists that is appropriate for use in children ages 1-4 years, an age group that is more commonly impacted by a number of childhood cancers. Thus, Dr. Gilchrist is finalizing the development of a scale of CIPN specifically tailored for young children that focuses on eliciting responses to test nerve function (such as tendon reflexes and strength of muscle groups) as well as developmentally appropriate measures of motor function (such as grasping an object or standing on one foot). She is also comparing results from 25 children ages 1-4 years being treated for cancer with neurotoxic treatments and 25 age and gender-matched controls to determine if the measure is both reliable and valid. If successful, she will be able to provide an objective measure for this common treatment side-effect that should positively impact both research and clinical care for these young children.

With increased survival for children with cancer, efforts that prevent long-term health problems are important for improving the quality of life and life expectancy of these children. Diet and fitness are two critical factors for healthy survivorship, but interventions for survivors of childhood cancer have had limited impact, focus almost exclusively on physical activity, and often exclude caregivers, the primary nutrition gatekeepers in the home. Although research supports a key role for the gastrointestinal (GI) microbiome in regulating weight and health outcomes, no studies have examined the “obesogenic” microbiome in the context of interventions for these survivors. Harvesting Hope for Kids (HH4K) is a unique, biobehavioral lifestyle intervention delivered over 8 weeks during the summer in a university-based, cancer survivor garden. It was adapted from a successful intervention for survivors of adult-onset cancer, with pilot data supporting its feasibility in children. In line with St. Baldrick’s mission to improve outcomes for children with cancer, this randomized controlled trial is evaluating the efficacy of HH4K to improve dietary and physical activity patterns in 40 survivors of pediatric cancer (i.e., ages 8-12; < 2 years off treatment). Results will support a larger, multi-institutional trial and improve survivorship care to prevent costly, long-term morbidity.

This award allows Dr. Parsons the freedom to pursue discovery without the restrictions of a normal grant. The questions he is exploring include: What are the biologically and clinically-relevant genomic alterations in high-risk and rare pediatric cancers? What are the most useful and cost-effective clinical sequencing tests for childhood cancer patients? How can clinical genomics/precision oncology be most effectively implemented for diverse patients and families in varied clinical settings? What clinical benefit can precision oncology approaches and the use of molecularly-targeted therapies offer to childhood cancer patients? He is optimistic that a "team science" approach, bringing together investigators from diverse disciplines, departments, and institutions, will continue to yield critical data and discoveries that guide pediatric cancer research and clinical care in the next decade.

Some childhood cancers do not respond to chemotherapy, surgery, or radiation. For these patients, researchers are developing a new set of treatments that use their own immune system to attack the cancer. To turn on these defenses, they need to bolster the DNA in 200 million immune cells, efficiently and safely. Unlike other strategies, these cells do not need to come from the patients, who are already weakened. Dr. Weiss has invented an engineering solution to do so and is testing it so that he can make this treatment widely available to patients and their doctors soon.

Ewing Sarcoma (ES) is a type of cancer growing in or around bones in children and young adults. A protein called CD99 is present on all ES cells and inhibition of CD99 by different means kill ES cells. As of today none of these methods of CD99 inhibition is available as a clinical tool. Dr. Uren's team recently discovered that an FDA approved drug, clofarabine, can do the same and kill ES cell by directly binding and blocking CD99. Since clofarabine is already FDA approved, it can be tested on children with ES immediately in a Phase II clinical trial. Clofarabine is currently used in leukemia patients in the clinic due to its ability to inhibit different proteins in the cell. Since his findings suggest that there is a novel mechanism that was not known before, it is critical to establish how exactly inhibition of CD99 in ES cells lead to their death. That knowledge is the key to initiate a Phase II clinical trial with ES patients. This project will provide the missing information and accelerate design of new clinical trials based on CD99 inhibition.

Medulloblastoma is the most common malignant brain tumor of children. New approaches to treatment are needed, because current treatment can cause brain injury and fails too many patients. Some medulloblastomas are driven by excessive activity of a signaling pathway called SHH, and for these patients, SHH-pathway inhibitors may offer new hope. Drugs that target an SHH-pathway protein called SMO work against other cancers in other parts of the body. However, medulloblastomas rapidly become resistant when treated with SMO inhibitors.

As the recipient of the Miracles for Michael St. Baldrick's Research Grant, Dr. Sokolsky-Papkov will make SHH-targeted therapy newly effective for medulloblastoma using two innovations. She will use a new combination of two FDA-approved drugs, vismodegib and palbociclib. These inhibitors disrupt two different points in the pathway connecting SHH signaling to tumor growth, preventing resistance that can develop when either drug is administered alone. Furthermore, she has developed a method of packaging these drugs into tiny particles called nanoparticle micelles, which can deliver increased amounts of each drug into brain tumors. Dr. Sokolsky-Papkov hypothesizes that the combination of palbociclib and vismodegib, delivered for the first time in nanoparticle micelles, will advance brain tumor treatment and bring new effectiveness to medulloblastoma therapy.

This grant is named for the Miracles for Michael Fund created in memory of Michael Orbany who was diagnosed with medulloblastoma when he was six years old. Even through treatment and relapse, Michael had unwavering faith and perseverance, wanting most to make others happy. This fund honors his tremendous strength to never ever give up.

Although patients with certain types of brain tumors are frequently cured by well-established treatments, patients that experience tumor relapse have limited treatment options and frequently succumb to their disease. In addition, the side effects resulting from radiation therapy result in lifelong and devastating cognitive impairment. As the recipient of the Making Headway Foundation St. Baldrick's Research Grant, Dr. Sarosiek recently found that decreasing the expression of BET proteins with a targeted drug can enhance the radiation sensitivity of brain tumors while reducing radiation sensitivity in healthy brain cells, thus supporting increased cure rates and decreased treatment-associated toxicities. In this project, Dr. Sarosiek is directly testing the sensitivity of medulloblastomas to BET inhibitors, alone and in combination with radiation therapy and chemotherapy; and determining the extent to which BET inhibitors can protect critical brain cells from radiation treatment. Importantly, BET inhibitors are currently being evaluated in clinical trials for other cancers and are thus readily available for clinical deployment for treatment of pediatric patients with medulloblastomas. Knowledge gained in these studies will serve as a foundation for the testing of BET inhibitors in clinical trials in children diagnosed with medulloblastomas and potentially other CNS tumors to dramatically improve treatment outcomes.

This grant is named for the Making Headway Foundation whose mission for the past 20 years has been to provide care and comfort for children with brain and spinal cord tumors through a continuum of services and programs while also funding medical research for cures. 

Millions of cells are formed every day in the developing brain of children. Medulloblastoma, a pediatric tumor, occurs when the proliferation of cells in the cerebellum (a lower part of the brain) becomes uncontrolled. The Notch pathway is a key mechanism that governs cell proliferation in many biological contexts. Aberrant up-regulation of Notch signals is associated with medulloblastoma. Re-gaining control of Notch could help cure medulloblastoma patients. As the recipient of the Hope for Daisy Research Fund for Pediatric Brain Tumors St. Baldrick's Research Grant, Dr. Rual's goal is to better understand the molecular mechanisms that control Notch signals in brain cells and, thus, to define novel therapeutic targets for the benefit of medulloblastoma patients. He recently identified the L3MBTL3 gene as a new modulator of Notch signals. Importantly, previous studies have shown that the L3MBTL3 genes is deleted in medulloblastoma patients. Dr. Rual hypothesizes that the L3MBTL3 deletions observed in medulloblastoma patients result in the aberrant regulation of Notch signals, thus supporting tumorigenesis. Dr. Rual's team will test this hypothesis by studying the extent to which inhibiting L3MBTL3 modulate medulloblastoma tumor progression in models of medulloblastoma. This study could offer critical mechanistic insights on the role of the L3MBTL3 in medulloblastoma that could be harnessed in the future for the therapeutic benefit of medulloblastoma patients.

This grant is funded by and named for the Hope for Daisy Research Fund for Pediatric Brain Tumors, a St. Baldrick's Hero Fund. Diagnosed with medulloblastoma at the age of six, Daisy Walsh met the challenge head on with joy, strength and laughter. Days before her eighth birthday, the tumor recurred and despite her brave battle, Daisy passed away in February 2020. This fund honors her courageous spirit by helping to raise awareness and funds for research to increase survival rates and hope for all children battling brain cancer.

The goal of Dr. Riehle's research is to find a cure for a rare form of liver cancer that occurs in children and young adults, called fibrolamellar hepatocellular carcinoma (FL-HCC). Unfortunately, surgery is currently the only effective treatment option for these patients, and once the disease has spread outside of the liver there is no chance for cure. Dr. Riehle's laboratory has spent the last few years trying to understand what changes within the liver cause healthy kids to get this cancer, and has developed a couple of new models of FL-HCC that can be used for drug screening. In this project she is using these models to test new treatment options and to try to understand how this cancer develops.

Cure rates for pediatric acute myeloid leukemia (AML) have remained at or below 60% for decades, and the largest reason for treatment failure is relapsed disease. Once relapse happens, it is very difficult to cure the disease. It is well known that interactions between AML cells and the non-cancerous supportive cells in the bone marrow, called stromal cells, can protect leukemia cells from chemotherapy. Dr. Redell's team reported that an enzyme in AML cells, called spleen tyrosine kinase (SYK), is turned on when AML cells contact stromal cells, and SYK helps AML cells survive chemotherapy. She will further investigate this enzyme, using a large panel of AML cells that come directly from pediatric patients. The drug company Gilead Sciences has given Dr. Redell a supply of their new SYK inhibitor, entospletinib, to test in her studies. To make sure that the results of the drug testing are related to blocking SYK, she also has made some AML cells that do not make SYK. Dr. Redell's team will do experiments to learn how SYK helps AML cells resist chemotherapy, and they will test entospletinib in AML models to determine if it might be a good drug to add to chemotherapy for patients.

Juvenile myelomonocytic leukemia (JMML), a fatal childhood blood malignancy, has limited therapeutic options. Relapse remains the main cause of treatment failure, most likely due to the persistence of leukemic stem cells (LSCs), a small population of self-renewing precursor cells that give rise to the bulk of tumor cells. Dr. Qu is exploring an innovative approach to eradicating LSCs in a subset of JMML that is caused by genetic mutations in Ptpn11. The information gathered from this study may yield a novel strategy for the treatment of this particular type of JMML.

Medulloblastoma is one of the most common malignant brain tumors in children. The Group 3 subgroup tumors have the poorest outcomes due to dissemination of tumor cells to distant sites in the central nervous system. As the recipient of the Benicio Martinez Fund for Pediatric Cancer Research St. Baldrick's Research Grant, Dr. Pei has identified a subpopulation of tumor cells that contribute to the metastasis after radiotherapy. He is determining whether targeting these cells can eliminate or prevent metastasis of Group 3 medulloblastoma, thereby improving the outcome of patients with this disease. 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. Despite complications from treatment and setbacks, Benny has an amazing can-do attitude and is battling the cancer with determination.

This grant is funded by the Hero Fund that honors Benny’s fight and supports cures and better treatments for kids like him.

Radiation therapy is an important tool in the treatment of childhood cancer. Radiotherapy not only makes tumors shrink, it also causes inflammation of the tumor and can make immune cells attack the cancer. However, tumor cells can secrete substances that prevent immune cells from killing cancer cells. In addition, certain immune cells, called regulatory T cells (Treg) and myeloid derived suppressor cells (MDSC), exist to prevent an overshooting immune response. These cells are recruited to inflamed tumor tissue and dampen the anti-cancer immune response. To overcome this problem, Dr. Otto is testing a drug in combination with radiotherapy that has shown to reduce or deplete immunosuppressive cells from tumors, and lead to increased numbers of cancer killing immune cells in the cancer tissue. In models of pediatric cancer, he is combining this drug with a particular form of radiotherapy, called radionuclide therapy that uses radioactive substances which are injected into the bloodstream to carry their radioactive load directly to tumor cells. Dr. Otto hopes that this combination therapy will lead to robust and long-lasting anti-cancer effects.

This grant is made with generous support from the Team Campbell Foundation, established in memory of Campbell Hoyt, who courageously battled anaplastic ependymoma, a rare cancer of the brain and spine for five years. Its mission is to improve the lives of families facing a childhood cancer diagnosis through raising awareness, funding research and providing psycho-social enrichment opportunities.

This year it is estimated that 800 children will be diagnosed with osteosarcoma. It is thought that sex hormones play a role in the onset of the disease, as more boys than girls get osteosarcoma and the cancer develops at the time of puberty. Dr. Miranda hypothesizes that a key molecule in estrogen signaling is turned off in osteosarcomas, preventing those cells from being normal bone. Her preliminary data shows that she can turn back on that key estrogen signaling protein. These drugs have not been tested in osteosarcoma patients, but are FDA-approved drugs, so they could provide a treatment for osteosarcoma patients in the immediate future.

This grant is generously supported by the Sweet Caroline Fund created to honor the memory of Caroline Richards who was diagnosed with osteosarcoma at age 11. She persevered through rigorous treatments with a giving spirit and a contagious smile, always thinking of how to make others happy or laugh. This fund pays tribute to her compassion for others by supporting osteosarcoma research to help kids with cancer

Rhabdomyosarcoma (RMS) is a cancer with features of skeletal muscle, and the most common soft connective tissue cancer of childhood. The alveolar variant of RMS (abbreviated ARMS) is particularly hard to cure. If we could figure out which proteins in ARMS cancer cells work together to drive this cancer, we might also be able to figure out which are good drug targets. A common genetic error in ARMS is the mutant protein PAX3-FOXO1, which turns on cellular programs that cause ARMS cells to keep dividing. However, PAX3-FOXO1 is not a good drug target, and it does not work alone – it physically interacts with other proteins that carry out its cancer-causing instructions. Here, Dr. Linardic and colleagues will use a sophisticated new method to identify proteins in PAX3-FOXO1’s cellular neighborhood, a rapid screening technology to figure out which are most crucial to ARMS, then use models of ARMS to see which of the proteins might be the best drug targets. Importantly, this project will be carried out by three research teams with unique but complementary skills working together, united in a mission to find new therapies for this difficult-to-cure cancer.

As the recipient of the Rosa and Francesco Romanello St. Baldrick's Research Grant, Dr. Lawlor is studying an aggressive tumor called Ewing sarcoma that occurs most often in teenagers. It usually starts in a bone and then can spread or metastasize throughout the body. Once it has spread, the chances of cure are very poor. She is studying how the tumor cells change the surrounding normal tissues to allow the tumor cells to leave the bone and spread to other sites in the body. Results so far have shown that the tumor cells and the normal tissues "talk to each other" and that this crosstalk is likely to be essential for the growth and spread of the tumor, both within the bone as well as in other tissues. Dr. Lawlor will decipher these messages, and the instructions they convey, so that new therapies can be developed that will intercept them and block tumor spread.

This grant is named in recognition of Salvatore Romanello for his decade of service as pro bono general counsel to the St. Baldrick's Foundation. He has chosen to name the grant in honor of his parents who instilled in him the values of generosity and caring for a greater cause.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor that has a very poor prognosis despite aggressive treatment. The development of new, effective therapeutic approaches for AT/RT has been hindered by a lack of specific therapeutic targets. It is necessary to find effective therapeutic targets, preferably based on the understanding of the molecular mechanisms that promote this highly malignant brain tumor. A tumor suppressor gene (SMARCB1) is absent in the majority of AT/RT and loss of this gene leads to factors that promote tumor growth. This research involving genetic and pharmacologic inhibition of histone binding proteins (EZH2 and BRD4) is of high importance for developing effective therapies for pediatric patients with AT/RT. Dr. Hashizume will determine whether therapeutic combination of targeting two histone binding proteins, BRD4 and EZH2, provides synergistic benefits, and will inform how best to maximize the clinical potential of combination therapy for effective treatment of children with AT/RT. This research will also test how tumors adapt to this molecular targeted therapy, to ultimately inform clinicians how to treat tumors that have resistance to molecular targeted therapy. Finally, this project will explore how this combination therapy interacts with radiation in treating AT/RT, which is important due to the frequent use of radiation in treating AT/RT.

This grant is generously supported by the “Just Do It…and be done with it” St. Baldrick’s Hero Fund created in honor of Sara Martorano who was four years old when she was diagnosed with Stage IV Wilms tumor. Thanks to research, today she is cancer free. This fund celebrates the courage of cancer kids through treatment and the support of their family and friends.

Although many children being treated for cancer initially respond to therapy, cancer cells often become resistant to chemotherapy drugs. Drug resistance is a major cause of cancer relapse, recurrence, and treatment failure. Dr. Gordon's goal is to identify new approaches to block, or reverse, resistance to an important class of cancer drugs. He has already identified one approach to reverse resistance in the laboratory, which he is now testing in models of cancer. Dr. Gordon is also testing a large number of additional drugs for the ability to prevent or reverse resistance.

The immune system acts as the body's defense against cancer by recognizing and attacking cancer cells. However, cancer cells have devised strategies collectively called "immune evasion," to thwart these protective mechanisms, making it difficult for immunotherapies to be fully effective.

As the recipient of the Emily Beazley Kures for Kids Research Grant, Dr. George aims to understand how the MYCN gene, which is abnormal in over half of patients with high-risk neuroblastoma, can cause tumor growth by shutting off protective immune mechanisms. In her preliminary studies, she has observed that MYCN amplification is associated with genes that evade the immune response, but exactly how MYCN does this is not known. Dr. George will use a novel model to understand how abnormal MYCN enables tumor cells to evade the immune system. At the age of 8, Emily was diagnosed with Stage III T-cell lymphoblastic non-Hodgkin’s lymphoma and battled through three relapses. Her family prayed for a miracle but discovered Emily herself was the miracle, inspiring a community to come together to show love and change lives. She had a dream of starting a foundation to fund research and named it “Kures for Kids”. Today, Emily's family and friends carry on her dream and her mission in her memory.