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Bone marrow transplantation is a highly effective treatment for relapsed and difficult to treat forms of pediatric leukemia, but unfortunately has a high risk for dangerous side effects. Viral infections are a major problem in the weeks and months after bone marrow transplant while children's immune systems are still immature. These infections can be debilitating and even deadly while also being very difficult to treat since available antiviral medications frequently do not work. Over the last few years, researchers have had great success in combating these viral infections by taking T-cells (a type of infection fighting cell that is part of the immune system) donated by children's personalized stem cell donors and engineering them to attack and kill certain viruses. Additionally, the rates of side effects using this therapy have been incredibly low. Dr. Rubinstein now intends to offer this therapy as a preventative measure, with the hope that this strategy will decrease the number of patients suffering from dangerous viral infections after bone marrow transplant. This clinical trial has the potential to decrease the number of pediatric cancer survivors who die from infection while also shortening hospitalizations and decreasing the need for other anti-viral medications. This grant is generously supported by the Rally for Ryan Fund, a St. Baldrick's Hero Fund. Ryan was diagnosed with ALL when he was 7 years old and began treatment immediately. Initially labeled “high risk” due to a poor response, he completed 3½ years of a difficult treatment protocol before relapsing 11 months later. After his third relapse and an unsuccessful immunotherapy trial, Ryan had a bone marrow transplant in December 2020. He is currently fighting graft vs. host disease but is doing well and is optimistic for a good response. The Campanaros created this Hero Fund to celebrate Ryan’s courageous spirit and knowing firsthand the importance of research, to raise funds to find better treatments for kids with cancer.

Based on progress to date, Dr. Reitman was awarded a new grant in 2022 to fund an additional year of this Fellow award. Brainstem gliomas are deadly brain tumors that affect children. The only effective treatment is radiation therapy, but despite this treatment all children with this disease eventually experience growth of the tumor and eventually death. As the Emily Beazley's Kures for Kids Fund St. Baldrick's Fellow, Dr. Reitman will test if treatments that enhance the efficacy of radiation therapy can improve survival in the laboratory. This could lead to new clinical trials aimed at helping children with brainstem gliomas to survive longer. This grant is funded by and named for Emily Beazley's Kures for Kids 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.

Over-expression of HOXA9 protein in acute leukemias, which are cancers of the blood, is associated with worse outcomes. This over-expression occurs in more than 50% of acute myeloid leukemia (AML) cases and in approximately 75% of infant acute lymphoblastic leukemia (ALL) cases. In the laboratory setting, decreasing the level of HOXA9 in AML cells has been shown to reduce their growth. This project aims to develop a way to target HOXA9 in AML and infant ALL using short segments of DNA called oligonucleotides designed to decrease HOXA9 protein or prevent its function. The use of oligonucleotides as drugs has recently been successful in the treatment of various disorders. The goal of these studies is to eventually lead to the use of oligonucleotides as novel therapeutic agents in a clinical trial setting for treatment of AML and infant ALL.

Leukemia is the most common form of childhood cancer. While most children with leukemia can be cured, patients whose leukemia comes back after an initial response to therapy are very difficult to treat and often die of their disease. As the Ty Louis Campbell Foundation St. Baldrick's Fellow, Dr. Levinson studies one of the classes of medicines used to treat leukemia called "glucocorticoids" (a type of steroid), in a type of leukemia called T-cell ALL. Though glucocorticoids are usually very good at killing leukemia cells, some patients have been found to not respond (or be "resistant") to glucocorticoids, while others develop resistance over time, making their disease far more difficult to treat. Dr. Levinson's research is focused on understanding how and why such resistance develops in an effort to identify ways to overcome it and, ultimately, increase the percentage of children with T-cell ALL who can survive their disease. This grant is funded by and named for the Ty Louis Campbell Foundation, a St. Baldrick's partner, created in memory of Ty Louis Campbell who lost his battle with brain cancer at the age of five. The Foundation seeks less toxic, more effective treatments that are specifically designed for children fighting cancer. Their ultimate mission is to help fund the intelligence and technology that will uncover new ways to cure children with cancer.

Based on progress to date, Dr. Conneely was awarded a new grant in 2022 to fund an additional year of this Fellow award. Acute myeloid leukemia (AML) is the second most common blood cancer in children and is difficult to cure. About one quarter of children with AML have a form of the disease called core binding factor (CBF) AML. Despite intense therapy, cancer will come back in one out of three children with CBF-AML. We want to find new ways to treat this common form of AML by learning how the specific combination of mutations in the cancer cells affect their ability to grow and survive. Some patients with CBF-AML have unique mutations that can stop cells from correctly fixing damage, allowing them to grow too quickly. The project will study how these mutations contribute to CBF-AML cells' development, growth, and survival, affecting the cancer cells' ability to grow using cancer cells with these unique mutations. This will help in understanding how this type of AML develops, and may lead to new ways to treat children with this disease. This grant is generously supported by Double Deckers Destroy AML, a St. Baldrick's Hero Fund. Joel and Seth were not only identical twins but best friends. In an ironic twist of fate, both boys were diagnosed with Acute Myeloid Leukemia just three months apart. With the overlapping diagnoses and treatments, the family was separated for months at a time and looked forward to days when they could be together at home. Joel and Seth both received bone marrow transplants and endured complications from the procedures. Sadly, both boys relapsed. Surrounded by their loving family, Joel died in November 2017 at the age of three, followed by Seth in May, 2019 when he was four years old. The twins were named as 2020 Ambassadors for St. Baldrick's so their story can continue to inspire many. The Double Deckers Destroy AML Hero Fund was established because the Decker family strongly believes more research is needed for AML, especially when the disease has relapsed. They want to support research so other families won’t have to say goodbye too soon.

There are new cancer therapies in which a patient's own immune system is retrained to fight against their cancer. In one of these therapies, known as CAR-T cells, a patient's immune cells are removed from the bloodstream and reprogrammed to target and attack their cancer when the cells are returned to the body. While this therapy has shown great promise, there are still situations, especially with very high-risk cancers, where it does not work. One significant issue that exists with this treatment is that the retrained immune cells do not always stick around after being given back to the patient, which allows the cancer to outlast the therapy and come back. We know that once cancers have resisted a treatment once, it is difficult to use the same treatment again. This projects aims to find ways to alter tumor-targeting immune cells to make them last longer when they are given back to patients, ultimately allowing for a long-term cure for their cancer without the need for further treatment. This grant is generously supported by the TeamConnor Childhood Cancer Foundation. TeamConnor Childhood Cancer Foundation's mission is to raise funds for national childhood cancer research programs, to build awareness that only a fraction of the NIH’s annual funding supports childhood cancer research, and to support inpatient programs. Founded in 2008 in honor and memory of Connor Cruse, TeamConnor has funded over $4M in pediatric cancer research grants across the United States.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Raman spectroscopy (RS) is used to characterize different types of cancer tissue. Usually RS fingerprints are obtained when a slice of cancer tissue is examined under a microscope. With a new design as a portable hand-held RS probe, the St. Baldrick's Foundation Summer Fellow will use the probe to determine RS fingerprints in cancer cell cultures. If successful, the project results could be used to design uses of the probe in the clinic setting to detect cancer cells in blood or other fluids.

This grant funds a medical student to complete work in pediatric oncology research for the summer. JMML is a rare type of childhood cancer that is really hard to cure. Right now, even our best treatments only stop this cancer for a year or so before it starts to come back. Cancers can be studied in specific models, which allow researchers to try out different drugs and treatments to see what works. The goal of this project is to use these models to find new treatments for JMML. This grant is named for the St. Baldrick's Foundation Staff whose generous gifts have helped fund this opportunity and may encourage students to choose childhood cancer research as a specialty.

This grant funds a student to complete work in pediatric oncology research for the summer. There has been little success in curing high risk AML patients, with survival rates remaining at < 25%. This highlights our current reliance on highly intensive cytotoxic therapies and stem cell transplant, and their inadequacies. This project studies the combination of novel target discovery with state-of-the-art stem cell expansion technology. Protein science provides a unique opportunity to generate one of the most impactful therapeutic discoveries in childhood AML in the last 40 years, with minimal toxicity. The summer intern will assist in investigating the impact of drugs on cancer targets while minimizing toxicity toward healthy cells. Results will be used to help identify critical genes involved in cancer growth and disease resistance, and to leverage future work in drug development.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Children with aggressive neuroblastoma have poor cure rates despite intensive treatment, and new therapies are needed. Treatments that inhibit important proteins and pathways in neuroblastoma tumors are likely to be more effective with fewer side effects. Kinases are proteins that control signals in cancer cells, leading to cancer cell growth and spread. This study proposes to test a certain inhibitor to determine its effectiveness against neuroblastoma cells and tumors. The results of these studies will determine whether BLU-667 is effective against neuroblastoma, potentially leading to clinical trials using BLU-667 for treatment of children with neuroblastoma.

This grant funds an undergraduate student and medical student to complete work in pediatric oncology research for the summer. T-cell acute lymphoblastic leukemia is a deadly childhood cancer that affects blood cells. The current treatment uses highly toxic medications. The goal of the proposed project is to test the efficacy of a novel, less toxic, targeted treatment for T-cell acute lymphoblastic leukemia. This award will train the student to perform experiments to test the efficacy of the novel treatment in T-cell leukemia and to determine the mechanisms of drug action against leukemia cells.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. This project will validate a drug for the medulloblastoma, a type of brain tumor, specifically tumors that spread from the original cerebellar location to the covering of the brain and spine (the meninges). This grant is named for the St. Baldrick's Foundation Staff whose generous gifts have helped fund this opportunity and may encourage students to choose childhood cancer research as a specialty.

This grant funds a student to complete work in pediatric oncology research for the summer. Osteosarcoma (OS) is the most common and highly lethal bone cancer affecting children and adolescent populations. New therapies are desperately needed for this highly aggressive disease, as outcome for metastatic OS has not improved over the past few decades despite the utilization of aggressive combination chemotherapy. The summer fellow will focus on testing a novel CA-IX small molecule inhibitor using syngeneic OS tumors in vitro and in vivo. Activities generated through this Summer Fellowship grant will lay the foundation for pre-clinical data for the use of CA-IX inhibitor in future clinical trials.

This grant funds a student to complete work in pediatric oncology research for the summer. This lab specializes in harnessing the power of a particular type of immune cells called macrophages and microglia which are the body's scavengers. This is done by blocking a "don't eat me" signal called CD47. The CD47 protein acts as a "don't eat me" signal to macrophages which normally engulf and devour cancer cells and other diseased and dying cells. It turns out that nearly every kind of cancer uses CD47 to evade these macrophages. Covering up the CD47 a "don't eat me" protein allows the immune cells to find and swallow cancer cells. Here we will test whether the ability of macrophages to eat tumor cells can be increased by blocking another immune dampening molecule called adenosine which is rapidly increased by tumor cells as they grow.

This grant funds a medical student to complete work in pediatric oncology research for the summer. Pediatric glioblastoma (p-GBM) is a lethal brain tumor that can affect children. This cancer is difficult to treat due to several factors, including the tumor's resistance to conventional therapies as well as the sensitivity of the surrounding healthy brain tissue. Children who undergo surgery to remove the brain tumor live an additional three to six years on average, though the quality of life may be low. Phosphoinositide 3-kinase (PI3K) is a protein family that normally regulates cell replication and survival. However, when it functions incorrectly, cells can experience unchecked growth and cause cancer. Inhibiting this protein family is a viable treatment option for cancer but blocking the whole PI3K family has severe side effects. It is imperative to understand each member of the PI3K family to better develop treatments that involve them.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. Diffuse intrinsic pontine glioma (DIPG) is a type of children's brain tumor that currently has no cure or effective therapeutic options. This proposal aims to understand whether the target drug of ONC201, ClpP, can be targeted using novel compounds representing new potential therapeutics in DIPG.

This grant funds two students to complete work in pediatric oncology research for the summer. The experience may encourage them to choose childhood cancer research as a specialty. Project 1: Neuroblastomas are an enigmatic cancer of childhood with subtypes that have extremely good or poor survival. Poor prognosis neuroblastomas contain normal immune cells that help tumors grow. Important questions are 1) what is the repertoire of immune cells in neuroblastomas at time of diagnosis, 2) how the interplay between normal and tumor cells changes when tumors recur. The Summer Fellow will analyze images of tumors at recurrence and compare to the diagnosis images. These findings will provide insights into the types of immune cells that cancer cells rely on and may allow identification of new targets of therapy. Project 2: Decline in brain function may happen after irradiation to the brain in children. It is hard to predict the extent and speed by which it happens. There is suggestion that more rapid injury happens in areas with iron deposition. Using a novel MRI method that allows chemical identification and quantification of iron in the brain, the Summer Fellow will characterize the imaging changes in white matter of the brain in children who have been treated with radiation for their brain tumors. This will allow to then correlate the changes with future outcome of their cognitive function.

This grant funds an undergraduate student to complete work in pediatric oncology research for the summer. DIPG's are the worst type of brain cancer children can get; there is no cure. This project will try a new approach to change that. Using large publicly available datasets from large experiments, 4 drugs have been identified that theoretically can slow down the growth of DIPG tumors. Researchers will test these four drugs against several DIPG models generated from patients. If results are positive, this could lead to new treatments for this deadly disease.

This grant funds a medical student to complete work in pediatric oncology research for the summer. This year it is estimated that 800 children will be diagnosed with osteosarcoma (bone cancer). The lab has identified a gene (WNT5B) that is too high in a subset of osteosarcomas. By making a cell line that removes WNT5B, the lab will compare its growth to the original cells and target this gene in those cancers that have it to design a specific targeted therapy.

Ewing Sarcoma (EwS) is an aggressive bone and soft tissue tumor occurring in children and young adults. Approximately 25-30% of patients already have metastases at diagnosis and in spite of aggressive treatment, the survival for patients with metastatic disease remains dismal. EwS is considered an immune cold tumor that is largely resistant to conventional immunotherapy. Alternative treatment approaches are sorely needed, particularly in patients with metastatic disease. Dr. Sorensen and colleagues are using three novel strategies for targeting EwS tumors: 1) Inhibiting an EwS specific fusion protein that drives EwS tumor development. 2) Targeting a surface protein called IL1RAP. 3) Recruiting natural killer (NK) immune cells to EwS tumors and priming them to attack the tumor. This grant is the result of a generous anonymous donation to fund Ewing sarcoma research, specifically. It is in honor of a teenager fighting Ewing sarcoma, and is named the St. Baldrick's - Martha's Better Ewing Sarcoma Treatment (BEST) Grant for All.