Grants Search Results

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.

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.

In the U.S., children with a blood cancer called Hodgkin lymphoma (HL) are usually treated successfully. Some of these children will suffer health problems several years later because of the treatment they received. Because of this, doctors use powerful imaging tools to identify patients who are likely to do well or not. Those who are likely to do well require less treatment and those who are less likely to do well can receive more treatment. But in low-income countries like Malawi, these tools are unavailable, and the children there often receive treatment that may be unnecessary. Scientists have found unique abnormalities in adults with HL that can tell us who is less likely to do well. Here, Dr. Ozuah is testing whether these abnormalities are present in children and could be used to decide how best to treat children with HL in low-middle income countries

Pediatric undifferentiated sarcomas are highly aggressive cancers that typically affect soft tissues of young children. Due to their uncertain classification and lack of molecular signature there are no standard criteria for diagnosis or treatment. With the Alan's Sarcoma Research Fund St. Baldrick's Research Grant, Dr. Antonescu is applying state of the art genomic methods to provide a detailed genetic characterization in these orphan cancers and investigating driving chromosomal translocations or mutations involved in their growth. These results will establish an objective classification of these tumors based on their genetic abnormalities and will provide potential therapeutic targets for further novel therapies. Furthermore these findings will inform the generation of faithful models for studying sarcoma formation and new drug development.

This grant is funded by and named for the Alan's Sarcoma Research Fund, a St. Baldrick's Hero Fund. Alan Sanders was diagnosed with a rare sarcoma in his hip at 17 months. He had an indomitable spirit and throughout his 4 ½ year battle with cancer, he was joyful, upbeat and pressed on courageously in spite of surgery and treatments. Today his family and friends carry on his legacy and his rallying cry, “Fight’s on!” in the battle against childhood cancer by funding sarcoma research.

Neuroblastoma is a cancer of the nervous system that causes aggressive disease in infants and young children, and the overall survival rate of high-risk (stage IV) patients is low. Ornithine decarboxylase (ODC) is a validated target in several cancers and we advanced the ODC inhibitor DFMO into neuroblastoma clinical studies. While promising, large quantities of DFMO are needed for patient treatments because about 80% of the drug is released into the urine. To improve the retention of DFMO in the blood, this study explores the combination of DFMO with an FDA-approved adjuvant. We expect that DFMO in the presence of this adjuvant will (a) increase the DFMO concentration in the blood and (b) induce more potent anti-tumor effects in neuroblastoma tumor-bearing mice. Since both DFMO and the adjuvant are FDA-approved drugs, this new regimen could rapidly advance to neuroblastoma clinical studies.

NUT midline carcinoma (NMC) is a deadly cancer that affects children and young adults, with a survival of less than 7 months. NMC is caused by a protein called BRD4-NUT that changes the structure of DNA in such a way that the DNA drives expression of cancer-associated genes that promote growth of NMC. Dr. French proposes to determine what is actually happening to the structure of the DNA that allows it to express the cancer-driving genes. There are two protein types he suspects are helping BRD4-NUT distort the DNA conformation; these are called HDACs and HATs. Dr. French's team will use state-of-the-art inhibitors that target specific HDACs and HATs to determine their respective roles and help identify novel therapeutics to treat this incurable disease.

In the U.S., children with a blood cancer called Hodgkin lymphoma (HL) are usually treated successfully. Some of these children will suffer health problems several years later because of the treatment they received. Because of this, doctors use powerful imaging tools to identify patients who are likely to do well or not. Those who are likely to do well require less treatment and those who are less likely to do well can receive more treatment. But in low-income countries like Malawi, these tools are unavailable, and the children there often receive treatment that may be unnecessary. Scientists have found unique abnormalities in adults with HL that can tell us who is less likely to do well. Here, Dr. Ozuah is testing whether these abnormalities are present in children and could be used to decide how best to treat children with HL in low-middle income countries

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.

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.

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 in Memory of 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.

Current cancer therapy is very toxic and does not always work. We have developed a way to deliver much more drug to the tumor, and much less to the patient, by packaging the drug in properly designed nanomedicines. These delivery systems take advantage of the fact that most aggressive tumors have leaky blood vessels, so our nanomedicines can pass through into the tumor, but they bypass most normal tissues. Using these formulations, we can deliver 10-100 times as much drug to the tumor, so we can use less total drug and still get better results. In addition, Dr. Brodeur is using a novel drug called SN22. Although SN22 is related to a commonly used chemotherapy agent called irinotecan, it is an active drug, and unlike irinotecan it does not have to be activated by the liver. It is not only much more potent but also harder for the tumor cells to get rid of. These features make SN22 much more therapeutically effective. The carrier Dr. Brodeur is using to make this nanomedicine can deliver four molecules of SN22 within each “packet” that enters the tumor. Because he can use less total drug, and because the nanomedicine can circulate for a long time with the drug attached, there is much less exposure to the rest of the body, so side effects are dramatically reduced. As the recipient of the Invictus Fund St. Baldrick's Research Grant, Dr. Brodeur's goal is to develop more effective but less toxic therapy to treat children with cancer, and he can accomplish that goal with this approach using nanomedicine-based drug delivery. The nanomedicines he is developing should be effective against many different solid tumors in children or adults and he hopes to bring them forward to Phase 1 clinical trials.

This grant is funded by and named for the Invictus Fund, a St. Baldrick's Hero Fund created in memory of Holden Gilkinson and honors his unconquerable spirit in his battle with bilateral Wilms tumor as personified in the poem “Invictus” by William Ernest Henley. His family hopes to fund cures and treatments to mitigate side and late effects of childhood 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.

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.

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.

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.

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.

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.

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.