Grants Search Results

Malignant rhabdoid tumor (MRT) and atypical teratoid/rhabdoid tumor (AT/RT) are rare but devastating childhood cancers. Most children diagnosed with MRT and AT/RT are under the age of two, and most will die from their disease despite intensive treatment interventions. New insights into what causes these cancers, and new therapies, are desperately needed. Genetically, MRT and AT/RT are simple cancers, caused by loss of just one gene called SMARCB1. If we are to understand and treat MRT and AT/RT, therefore, we need to understand how loss of SMARCB1 causes cancer. As the recipient of the Oh Danny Boy I Love You So: The Danny O'Brien Rhabdoid Tumor Research Fund St. Baldrick's Research Grant, Dr. Tansey is working on an innovative molecular mechanism through which loss of SMARCB1 causes MRT and AT/RT. He proposes that these mutations drive cancer by stimulating the activity of a known pro-tumorigenic gene called MYC. Dr. Tansey further proposes that MRT and AT/RT can be effectively treated by drugs that block the actions of MYC, currently being developed by us and others. He is testing this model and exploring its therapeutic implications. Completion of this work has the potential to transform the understanding of how MRT and AT/RT form and how they can be treated. Danny O’Brien was five months old when he was diagnosed with a rare malignant rhabdoid tumor on his liver. Despite treatment to shrink the tumor, he passed away at the tender age of 9 months. Fortunately, he knew nothing but love and affection for all of his short life. This fund honors Danny’s courage and remembers his unconditional love in the midst of his battle with cancer.

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.

Nearly half of all children diagnosed with Acute Myeloid Leukemia (AML) will suffer a relapse after initially successful treatment. Whereas therapy efficiently clears the bloodstream of leukemia cells, frequent evidence of residual drug resistant disease points to a leukemia protective role of the bone marrow microenvironment. The mechanism by which the bone marrow acquires these protective abilities is not clear. Dr. Kurre recently observed that so called stroma cells, that provide bone marrow structure and support are functionally altered. Pilot studies conducted by Dr. Kurre also identified a new mechanism by which AML changes these stroma cells. In this project Dr. Kurre is studying pediatric AML samples to understand how the altered stroma protects leukemia cells from the effect of drugs commonly used to treat children with AML. The long term goal is to develop treatment approaches that reduce the burden of relapse, by maintaining initial remissions in children with AML, and without further escalating drug toxicity. Awarded at Oregon Health and Science University, and transferred to The Children's Hospital of Philadelphia.

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.

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.

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.

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.

Neuroblastoma is a cancer formed in certain types of nerve tissue and is the most common pediatric solid tumor outside of the brain. It is the leading cause of cancer-related death in children under five years old. Those patients who do survive often develop long-term side effects from intensive chemotherapy and radiation therapy. Thus, we need to develop better, safer alternative therapies for neuroblastoma. Dr. Cripe is currently studying the use of genetically modified herpes viruses. These viruses, which include the recently FDA-approved herpes virus T-VEC, can selectively infect and kill cancer cells without harming normal cells. In addition, these viruses are also able to enhance the patient's immune response against the cancer cells, potentially leading to a systemic and long-lasting protective immunity against cancer dissemination and recurrence. In the course of his studies, Dr. Cripe found that tumors infected with virus induce a counter measure by attracting cells that suppress immunity. In this study, he will test if he can improve therapy by interfering with that counter measure. If successful, these results may lead to a novel clinical trial for neuroblastoma patients.

Leukemia is a blood cell cancer that frequently affects children. Despite the advances in treatment options, children with certain subtypes of leukemia are resistant to current therapy. Novel therapy for childhood leukemia is urgently needed. Dr. Fang's team recently found a protein, whose name is GPR68. They found that the levels of GPR68 were increased in blood cells of leukemia patients. When they decreased GPR68 levels, leukemia cells died, suggesting that increased GPR68 helped leukemia cells survive. Interestingly, normal blood cells with reduced levels of GPR68 were normal, suggesting that only leukemia cells need GPR68. Dr. Fang's findings suggest that lowering GPR68 levels or limiting its function may help cure leukemia without injuring normal blood cells. As the recipient of the Emily Beazley's Kures for Kids Fund St. Baldrick's Research Grant, she will be working to understand the function of GPR68 in leukemia cells and normal blood cells, and test drugs that could cure leukemia by inhibiting GPR68 function. This grant is funded by and named for Emily Beazley's Kures for Kids Fund, a St. Baldrick's Hero Fund. 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.

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.

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.

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.

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.

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.

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.

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. 

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.

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