Grants Search Results

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

Do you ever get a cold sore on your lip, or know someone who does? That sore is caused by a virus that destroys the cells in your lip. As the virus spreads, the sore gets bigger. Viruses are great at killing cells and spreading. But, the sore eventually goes away because the immune system attacks the infected cells, killing them and stopping the viral infection, allowing your lip to heal. Imagine if we could get both the virus and the immune system to kill cancer cells instead of lip cells! Previously Dr. Haworth's team used a safe version of the cold sore virus to infect a common type of hard-to-treat childhood cancer cells. The virus directly killed cancer cells and caused the immune system to attack the cancer cells that the virus missed. Dr. Haworth's team is testing ways to make the virus and immune system work better together. Dr. Haworth is infecting model tumors with the virus, and giving immune cells designed to attack the tumor, hypothesizing that giving both virus and immune cells will cure the tumor. Awarded at The Research Institute at Nationwide and transferred to St. Jude Children's Research Hospital.