Grants Search Results

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

Diffuse intrinsic pontine glioma, also referred to as brainstem glioma, is a pediatric cancer that accounts for the majority of deaths from brain tumors in children. Although radiation therapy is the standard of care for brainstem gliomas, the median survival of children with this tumor type is less than one year from diagnosis. In order to improve the treatment of these patients, Dr. Kirsch's team is using a model of brainstem glioma that can be used to evaluate the effectiveness of new therapies. Using this model, they are testing whether removing a protein called ATM, which is the target of drugs now entering clinical trials, will enhance radiation sensitivity in brainstem gliomas. They hypothesize that deleting this target, when given in combination with radiation therapy, will increase the number of tumor cells killed by radiation and will therefore improve survival in brainstem gliomas when they have a specific gene mutation commonly found in this childhood brain tumor. If successful, these studies will inform the design of future clinical trials testing this strategy in children with brainstem gliomas.

This grant is named for Hannah’s Heroes, a St. Baldrick’s Hero Fund created in honor of Hannah Meeson and pays tribute to her fight by raising awareness and funding for all childhood cancers because kids like Hannah “are worth fighting for.”

Diffuse intrinsic pontine gliomas (DIPG) are lethal pediatric brain tumors with no treatments. In order to develop cures we need to understand their biology. Cancers survive on fuel to generate energy to support their uncontrolled proliferation. One of the fundamental nutrients that drive the energy production is the amino acid glutamine. How glutamine is taken up and metabolized by DIPG tumor cells is not know. Further it is not known if inhibiting cancer cells from taking up and metabolizing this fuel is therapeutic. To address this significant gap in our knowledge, Dr. Venneti is studying glutamine metabolism in DIPG cancer cells and evaluating inhibition of glutamine metabolism as a potential therapeutic strategy. This grant is made with generous support from the McKenna Claire Foundation established by the Wetzel family in memory of their daughter, McKenna. Their mission is to cure pediatric brain cancer by raising awareness, increasing community involvement and funding research.

High grade gliomas (HGG) are a vicious subtype of pediatric brain tumors that remain the leading cause of death among children with cancer. New therapeutic strategies are urgently needed to combat this scourge. By mining genomic datasets from HGGs, Dr. Walensky's team has identified a unique susceptibility profile based on retention of wild-type p53 status and dual expression of the negative regulators HDM2 and HDMX. Whereas p53 can be mutated or deleted to avoid cell cycle arrest or apoptosis, a frequent alternative mode of p53 suppression relies on overexpression of HDM2 and HDMX. Small molecules have been developed to target HDM2 specifically, but co-expression of HDMX causes resistance. Only a stapled peptide modeled after the critical p53 transactivation helix is capable of blocking both HDM2 and HDMX, a feature that has prompted its advancement to Phase I/II clinical trials in adult cancers.

As the recipient of the St. Baldrick’s Research Grant with generous support from the Team Campbell Foundation, Dr. Walensky is testing a novel therapeutic strategy for pediatric HGG based on a dual-targeting stapled peptide inhibitor of HDM2/HDMX. He believes that the proof-of-concept data to emerge could provide a compelling rationale for conducting a clinical trial in these otherwise rapidly fatal pediatric brain cancers. The Team Campbell Foundation was created in memory of Campbell Hoyt who passed away from Anaplastic Ependymoma. Their mission is to improve the lives of families facing a childhood cancer diagnosis through raising awareness, funding research and providing psycho-social enrichment opportunities.

Recently the Meshinchi lab discovered that mesothelin, a cancer-specific antigen, is highly expressed in a subset of childhood AML cases, a result that both highlights the distinct genetic differences between adult and pediatric cancers and opens the door for the development of more targeted therapies. Dr. Kolb is developing novel combinations of bispecific T-cell engaging antibodies, called SMITEs (Simultaneous Multiple Interaction T-cell Engagers) that will co-target mesothelin and the AML marker CD33. These T-cell engaging protein pairs physically link cancer cells to cytotoxic T-cells resulting in more potent and selective killing than single agents alone.

Adolescent and young adult (AYA) cancer survivors have an elevated risk of medical problems that can impact the quality and length of their lives, but few studies have focused on the occurrence of late medical conditions in this population. Using data on nearly all AYA cancer survivors in California, the Rich and Weissman Family Lymphoma Survivorship Fund St. Baldrick's Research Grant is identifying how often specific late medical conditions occur and how the risk of these medical conditions vary by clinical and patient factors. The results of the study will identify subgroups of young patients at increased risk of serious medical conditions, information critical to improving survivorship care and outcomes. Jared Weissman is a Hodgkin’s lymphoma survivor thanks to a clinical trial made possible by research. This Hero Fund honors his survivorship and his grandparents, Terri and Barry Rich, by funding research for new treatment options for cures and less toxic after effects for survivors.

Many cancer treatments kill both normal and cancer cells. Drugs used in standard cancer treatments have long term effects in children, such as causing developmental delays or second cancers later in life. Dr. Blackburn's team is working to find new drugs that kill cancer cells, but do not affect normal cells. By discovering characteristics that are unique to cancer and finding a drug that recognizes that specific characteristic, they will be able to selectively kill cancer cells. Their research goal is to improve cancer treatments so that children can live long, normal lives after their cancer is cured.